The heart is composed of four compartments: two atriums and two ventricles. The blood that reaches the heart first accumulates in the atriums. From here, it is sent to the ventricles. Afterwards, it is redistributed to the body by the contractions of the ventricles. The harmony of this process depends on the electrical currents in our hearts.

How is the electrical current formed?

There is a particular region in the heart called the sinus node. The sinus node is strip of a muscle that is 15 mm in length, 3 mm in width, and 1 mm in thickness, and is located in the right atrium of the heart. The cells of this strip are responsible for producing electrical currents, and are created in a different fashion from the rest of the cells that are responsible for producing contractions. This is where the electrical currents in our hearts are periodically produced. Every cell in the body contains elements such as sodium, calcium, potassium and chlorine that are electrically charged. The elements which are electrically charged are called ions. These ions also exist in the extracellular environment. The intra cellular and extra cellular concentrations of these ions are different from each other. This situation causes a difference in the electrical potential between the interior and exterior of a cell. This difference is called a membrane potential. Periodically, the membrane potentials of the sinus cells show sudden jumps – meaning they suddenly increase and then suddenly decrease. Since the cells are in close contact with each other, such a jump in the membrane potential of one cell triggers a jump in the membrane potential of another cell. The electrical currency that enables the contraction of the heart is produced by this continuous triggering of cells. On average, 70 electrical currents per minute are produced in the sinus node. These currents start being produced while a person is in the womb of their mother and continues their whole lifetime. The heart of an embryo starts beating while it is only 22 days old. However, the height of the embryo at this point has not even reached 1 cm. Isn’t it an amazing force that creates the beating heart of such a small embryo and keeps it going a lifetime?

How is the electrical current distributed?

Another node called the atrio ventricular node was created in between the atriums and ventricles in our heart. While the current coming from the sinus node is spread to the whole of the atrium, it is by this node that the current is sent to particular fibers. The task of this node is to hang on to the current coming from the sinus node for a while. Why does the current need to be held on to? Because blood can only enter the ventricles while it is resting and by holding on to it, the contraction of the ventricles is disabled while the contraction of the atriums is taking place. By this process, the blood coming from the atrium can enter the ventricle. Therefore, the blood fills in the ventricles and can be distributed throughout the body. The blood circulation is enabled in a flawless manner by allowing the atriums to do their duty while the ventricles wait.

After passing through the atrio ventricular node, the electrical currency eventually goes through the purkinje fibers. These fibers surround the ventricles like a web and are composed of cells that can conduct electrical current in a very fast manner. Compared to the atrio ventricular node, the electrical current can be conducted 150 times faster in the purkinje fibers. Therefore, the current reaches every point of the ventricles in a very short period of time. Every muscle in the ventricles contracts in a time shorter than one tenth of a second.

The muscles in the ventricles rapidly contract, one by one, depending on when the current reaches them. The contraction starts at the end of the ventricles and carries on towards the main veins exiting the heart. By this orderly and harmonious contraction, the blood is pumped from the end of the heart towards the main veins exiting the heart to be distributed among the body. Because all the ventricle muscles are stimulated very fast, the contraction also happens very fast, resulting in a strong pumping effect. The design of this system is incredibly wise, right down to its most minute detail.

Movement in heart muscle potential

As all cells in our body, the cells in the heart also have a membrane potential. We had stated before that this membrane potential is the result of the difference in intra and extra cellular ion concentrations. The charges of these ions are different from each other. For example, sodium and potassium have plus one (+1) charges, calcium has a plus two (+2) charge, and chlorine has a negative one (-1) charge. The resting potential of a cell is negative. This means that there are more negative ions within the cell when compared to its environment. Sodium, calcium, and potassium ions are mobile through the membrane. While sodium and calcium have a higher concentration outside the cell, potassium has a higher intra cellular concentration compared to its environment. There are channels created on the cell membrane that allow ions to pass through the membrane. The sudden increase in the membrane potential that was explained before causes a sudden rush of sodium ions inside the cell. This is such a rapid movement that it is concluded in a tenth of a second. Right after the entrance of the sodium ions, calcium ions also enter. Because these ions are positively charged, the membrane potential becomes positive.

With the entering of calcium ions into the cell, calcium ions are also released from the storages within the cell. By triggering the protein necessary for these contractions, the calcium ions become a means for the contraction of the heart muscles. Meanwhile, the potassium channels open and these ions within the cell pass to the extra cellular environment. The loss of positive ions results in the membrane potential being negative again. Therefore, the sudden jump in membrane potential that is the basis for the electrical current is created.

However, at this point there are extra amounts sodium and calcium within the cell and extra amounts of potassium outside the cell. The concentrations need to be returned to their original values for the next jump in the membrane to be possible. This task is given to a protein called the sodium-potassium pump that pumps out sodium from the cell and pumps in potassium. If this pump had not been created, the ion balance in any of the cells within the body would be impossible to re-establish. As a result, the life of the cells would come to an end. However, because of the remarkable intricacy of our cells, life is made possible for us.

Afterwards, some amount of the calcium ions are pumped out of the cell with a similar pump, while the rest are stored within the cell. The decrease in the concentration of calcium relaxes the muscle. Now the heart muscle has gone into relaxation and therefore is ready for the next contraction.

If the movement of the ions becomes unbalanced, the rhythm of our heart is disturbed. The unbalance in the ion movements or blockage in heart veins can be reasons for heart rhythm disorders. Even small heredity-based defects in the ions pumps affect the movement of these ions and can cause heart rhythm disorders. This situation shows that nothing is created by coincidence.

Movement in the sinus node

The jump in the membrane potential of a heart cell depends on the membrane potential jump of the previous cell. Through the gaps in between the cells that are in contact with each other, the positive ions that exit a cell reach the membrane of the cell next to it and trigger the opening of its ion pumps. As a result, the membrane potential of that cell starts changing. At this point, you may have this question: how does the electrical current start in one end of the sinus node that is not previously triggered by any cell?

This concept is explained by the ion transfer mechanism of the node cells being different than the muscle cells. Before explaining this, it should be noted that even while resting, a mechanism for allowing an ion exchange of the cell with its surrounding has been created. In the node cells, this exchange while at rest has been created in a way that the sodium and calcium exchange is larger and the potassium exchange is lower compared to the muscle cells during resting conditions. Therefore, the membrane potential of the node cells is less negative and slowly increases with time. As a result of this slow but steady increase, after a while it reaches a threshold. When it reaches it, the calcium channels in the membrane suddenly open and there is a rush of calcium ions into the cell. Thus, the jump in the membrane potential is created independently from another cell.

As it can be observed, even a single contraction of our heart depends on a very detailed, delicate, and complex system. Moreover, this system is repeated over a hundred thousand times within one day. After reflecting on this, how can we claim this system runs by coincidence or chance?

Today, more than 1 billion people are suffering from the lack of potable water. About 2.3 billion people (41 percent of the earth’s population) live in regions with water scarcity; this number is estimated to be 3.5 billion by 2025.1

96.5 percent of the world’s water is found in seas and oceans, and the remainder is found as ice caps, brackish water, and fresh water sources (e.g. lakes, rivers, and ground waters). To overcome water shortage problems, methods such as water conservation and dam construction have been applied for several years, but they are not enough against increasing water demand and decreasing fresh water sources.2

Water is also very important for generating energy, and vice versa. The largest portion of U.S. electric production is provided by thermoelectric power generation, where steam-driven turbine generators are used to generate electricity. In 2000, thermoelectric power plants used 39 percent of all fresh water sources in the United States.3 All these reasons make the production of drinking water a worldwide issue.

Desalination

Since most of world’s water supply is found in oceans and seas, desalination is the process of removing salts and minerals from either ocean or brackish water to make it safe for human consumption and use. The most widely applied desalination processes are divided into two main categories, thermal distillation processes and membrane processes.

Desalination via thermal distillation methods, which separate liquid mixtures based on their boiling points, mainly fall into three categories: multi-stage flash (MSF), multi-effect distillation (MED), and mechanical vapor compression (MVC). Thermal distillation processes require the evaporation of water while leaving the salt in a concentrated brine. Middle Eastern countries mainly use thermal-based desalination plants to produce fresh water because of their easily accessible fossil fuel sources.2, 4

Membrane-based separations are the main choice of producing potable water in countries outside the Middle East. More than 50 percent of the newly installed desalination plants have been using reverse osmosis (RO) membrane technology (since 2001).2

Membrane separations

A membrane is an interphase between two adjacent phases acting as a selective barrier, regulating the transport of substances between the two compartments. It is a very thin film that allows passage of some types of substances while preventing the passage of other substances, depending on their sizes. Membranes used for separation technology gave rise to an interdisciplinary area including many fields of science and engineering such as chemistry, chemical engineering, material science, process engineering, environmental science, ecology, and economics.5, 6 Today, the membrane industry is impressively large. The membrane separation technology market is quite diverse and ranges from medicine to the chemical industry, and the most important markets are medical devices and water treatment. There was a $2 billion sale of synthetic membranes worldwide in 2003.6

Water purification membranes

Water treatment processes employ several types of membranes. They include microfiltration (MF), ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) membranes. They are designed to remove materials of increasing sizes. MF membranes have the largest pore size and typically reject large particles and various microorganisms. UF membranes have smaller pores than MF membranes and, therefore, in addition to large particles and microorganisms, they can reject bacteria and soluble macromolecules such as proteins. RO membranes are effectively nonporous and therefore exclude particles and even many low molar mass species such as salt ions, organic substances, etc.7 NF membranes are relatively new and are sometimes called “loose” RO membranes. They are porous membranes, but since the pores are ten of angstroms or less, they exhibit performance between that of RO and UF membranes.8 Of these membranes, NF and RO membranes constitute the dominant technology for desalination of water.9

2.1 Nanofiltration Membranes

Membranes for nanofiltration (NF) are usually comprised of cellulose acetate or aromatic polyamides. NF allows diffusion of organic compounds, and rejects some salts with low pressures being applied. NF itself cannot purify seawater to drinking water standards, but it is a process that can be used to produce mildly salty water, or as a water-softening technique.2, 4 When NF is coupled with RO, then it can be used to turn seawater into drinking water.10

Nanofiltration membranes usually have negative charges (e.g., carboxylate groups, sulfonate groups, etc.), and as a result, ion repulsion is a major factor in determining salt rejection. More highly charged ions, such as sulfate, are more highly rejected than monovalent ions, such as chloride, by a negatively charged nanofiltration membrane. In particular, NF membranes are used to remove divalent ions such as calcium and magnesium, which are mainly responsible for water hardness. These membranes also usually display good rejection of organic compounds with molecular weights above 200 to 500 grams.2,11,12

2.2 Reverse osmosis membranes

Osmosis is a natural process in which water molecules move across a semipermeable membrane from a lower solute concentration area to the higher solute concentration area. Water flows until a chemical potential equilibrium of water is established. When equilibrium is reached, the pressure difference between the two sides of the membrane is equal to the osmotic pressure of the solution.12

Reverse osmosis (RO) is the process of forcing water from a region of high solute concentration through a membrane to a region of low solute concentration by applying a pressure that is greater than the osmotic pressure. As a result, separation of water from the solution occurs as pure water from the high concentration side to the low concentration side. The RO process includes a feed water source, feed pre-treatment, a high-pressure pump, RO membrane modules and post-treatment steps.

RO membranes are capable of rejecting monovalent ions such as sodium and chloride, which makes the RO process a valuable method for desalination. Membranes used for RO processes have salt rejections of more than 99 percent. RO membranes do not have distinct pores, but rather rely on free volume within the polymer film.

RO membrane separations depend highly on the properties of the polymer film such as the chemical and physical structure of the membrane material. Desired RO membranes should be resistant to chemical substances and microbial organisms, stable over a long time both mechanically and structurally, and have ideal separation properties such as high water flux, high salt rejection, chlorine, and fouling (clogging of membrane pores) resistance.

Approximately one billion of six billion people in the world live in water-stressed areas, and RO membrane technology is the leading desalination technology to overcome the problem of insufficient clean water and estimated to continue its leadership in the near future.13 Scientists and engineers are extensively investigating the development of the most efficient membrane desalination technology to produce the cheapest potable water.

On the other hand, cells use membranes, though scientists do not try to further develop them, since they were already designed in a perfect manner. Cellular membranes have a phospholipid structure with embedded proteins. They control many different kinds of transportations of substances in and out of cells (e.g. sugar, drugs, ions). They are so well designed that they know which substances are helpful or harmful for the cell, and decide on the passage of substances based on that. Many researchers have tried countless times for many years to produce an equally wonderful membrane technology for making clean water. But cellular membranes, consisting of hundreds of functions in living organisms, do not form spontaneously.

REFERENCES

1) R.F. Service, Freshwater resources, desalination freshens up. Science, (2006). 313, 1088- 1090.

2) L.F. Greenlee, D.F.Lawler, B.D. Freeman, B. Marrot, P. Moulin, Reverse osmosis desalination: Water sources, technology and today’s challenges. Water Research (2009), 43, 2317-2348.

3) T.J. Feeley, T.J. Skone, G.J.Stiegel, A. McNemar, M.Nemeth, B. Schimmoller, J.T. Murphy, L. Manfredo, Water: A critical resource in the thermoelectric power industry.Energy (2008), 33, 1-11.

4) G. A. Tularam, M. Ilahee, Environmental concerns of desalinating seawater using reverse osmosis. J. Environ. Monit.(2007), 9, 805–813.

5) P. Vandezande, L. E. M. Gevers, I. F. J. Vankelecom, Solvent resistant nanofiltration: separating on a molecular level. Chem. Soc. Rev.(2008), 37, 365–405.

6) M. Ulbricht, Advanced functional polymer membranes. Polymer (2006), 47, 2217–2262.

7) R.H. Perry, D.W.Green, Eds., Perry’s Chemical Engineers’ Handbook, 7th ed., McGraw-Hill: New York, 1997.

8) Sagle, A., and B. Freeman, “Fundamentals of Membranes for Water Treatment,” in The Future of Desalination in Texas: Volume 2, Report Number 363, Texas Water Development Board, Austin, TX, pp. 137-154 (2004).

9) H.B.Park, B.D.Freeman, Z.Zhang, M.Sankir, J.E.McGrath, Highly Chlorine-Tolerant Polymers for Desalination, Angew. Chem. Int. Ed. (2008), 47, 6019-6024.

10) N. Hilal, H. Al-Zoubi, N. A. Darwish, A. W. Mohammad, M. Abu Arabi, A comprehensive review of nanofiltration membranes: Treatment, pretreatment, modelling, and atomic force microscopy, Desalination (2004), 170, 281-308.

11) A. Gorenflo, D. Velazquez-Padron, F.H. Frimmel, Nanofiltration of a German groundwater of high hardness and NOM content: performance and costs. Desalination (2002), 151, 253-265.

12) M.E.Williams, A Brief Review of Reverse Osmosis Membrane Technology,EET Corporation and Williams Engineering Services Company, Inc., Harriman, TN, 2003.

13) K. P. Lee, T. C. Arnot, D. Mattia, A Review of Reverse Osmosis Membrane Materials for Desalination – Development to Date and Future Potential. J. Membr. Sci. 370 (2011) 1-22.

For the sake of simplicity, the very complex – yet flawless – organization of a single cell can be portrayed as a city. Even in a very small city that has a relatively low population there are different establishments of various sizes and capabilities that work in concert. Likewise, in order to keep the cell alive the intracellular organelles and proteins of a cell complement each other’s functions. Even though the majority of cities may have the resources to supply themselves, they also need to import and export goods. In addition, some cities may have greater industrial, residential, or agricultural strengths, making it necessary for it to communicate and trade with neighboring towns to eliminate shortages. In a similar way, cells have to communicate with neighboring cells, and bring in new sustenance and get rid of waste at different stages in their life cycles. In this article we will focus on one of the key elements of the import mechanism that is used by living cells, endocytosis.

Endocytosis is the process by which cells take in substances from outside. Since living cells are surrounded by a membrane, the cargo molecules, which are too large to penetrate through the membrane, have to be internalized by different means; this can be classified as Cell eating (i.e. phagocytosis: the endocytosis of large solid materials), cell drinking (i.e. pinocytosis: the endocytosis of liquids in large amounts) and receptor mediated endocytosis (the internalization of molecules that have specific receptors on the cell membrane) (Figure 1). During the course of these events, the portion of the cell membrane that surrounds the cargo is also internalized. However, at the present time, very little is known about the mechanisms that cause the cell membrane to invaginate and eventually be pinched off during the onset of endocytosis. Here we will concentrate on receptor mediated endocytosis, which has been intriguing biologists for more than three decades now.

Receptor molecules, which are located on the outer surface of living cells, function like receiving docks for cells. These are sites where the membrane-encountering molecule is first engaged. The cargo molecules, which arrive at the receiving docks, are often known as ligands (Latin ligare = to bind). Ligand molecules are either secreted from a neighboring cell or come directly from the bloodstream and can bind to the specific receptor molecules on the cell surface. In most cases the ligand is either a signaling molecule, which transmits information to the cell from the extracellular milieu, or a nutritious substance that needs to be internalized via endocytosis.

Unlike other forms of endocytosis, receptor mediated endocytosis occurs in a very controlled way. First of all, the ligand determines whether endocytosis will occur or not. Basically, a ligand molecule that does not have a corresponding receptor on the cell membrane cannot interact with the cell and, as a result, will not be internalized. For instance, a certain virus, which can cause severe lesions in the mouths of horses, cannot infect human cells, as our cells do not have the receptors that link the virus to the cell membrane. Secondly, the ligand cell determines how much intake will take place. That is, cells can control the amount of receptors on their membranes and thus how much the ligands that are recognized by these receptors will be internalized. By acting in this way, cells can adapt to different conditions by controlling the rate of endocytosis through the receptor molecules. The third way of control is concerned with the size of the molecules that are to be internalized. As we will discuss below, receptor mediated endocytosis is performed via some scaffold proteins that form cages (i.e. coats) around the membrane. These cages are fairly small in size, and molecules that are larger than 100 nanometers (100 nanometer is one-thousandth of the thickness of a human hair) cannot fit into them nor enter the cells along this pathway.

The conformation of the plasma membrane changes substantially during endocytosis. Given that the cell membrane has a fluidic nature, it must be accompanied by a firmer construction in order to perform these structural modifications. In the case of receptor mediated endocytosis, this function is carried out by clathrin cages (or clathrin coats), which are formed adjacent to the membrane. The clathrin protein is a three-legged molecule which can freely diffuse inside the cell. However, when a ligand molecule binds to a receptor on the membrane then multiple clathrins aggregate into that region and polymerize into cages composed of pentagons and hexagons (Figure 2a). These cages surround the cell membrane, compelling it to engulf the cargo (ligand) by invagination. When the cargo is entirely enclosed by the membrane a scission protein seals off the enclosed cargo from the plasma membrane (Figure 2b). The completely internalized membrane pouch rapidly casts away its clathrin coat with a quick uncoating reaction. After this point, the membrane pouch, including the cargo, can be transported to the inner compartments of the cell. In living cells, this process takes a little less than a minute. Even though the lifetimes of the clathrin coats are not very long, scientists have found ways of ascertaining the detailed organization of these molecules.

One of the most intriguing findings about the clathrin scaffold (or coat) is its breathtaking geometry. X-ray crystallography studies showed that the cages formed by the polymerization of multiple clathrin proteins are composed of pentagons and hexagons (Figure 3a). It has been also shown that in the majority of the cases the three dimensional structures of the cages are very similar to a soccer ball, where 12 pentagons are accompanied by 20 hexagons in order to create a curve (Figure 3b). However this is not the only geometry that clathrin coats can have. Electron microscopy images taken on frozen cells reveal that clathrins can also form some large flat arrays on the membrane which look exactly like honeycombs. In this configuration the pentagons are missing and all the clathrins align in the hexagon geometry to preserve a flat surface (Figure 3c).

The function of the honeycomb-shaped flat clathrin arrays is still a mystery. All we know is that they are more durable than the cages. In other words, although they do not have definite sizes like cages, they last much longer. Some scientists believe that these structures might be functional in the internalization of huge cargo molecules, such as bacteria, however, these claims still need to be proved. More research is needed if scientists are to be able to better understand clathrin-based endocytosis. Nevertheless, the fact that a simple geometrical modification at the molecular level can alter the entire mechanism of a biological process is on its own a very fascinating discovery.

Hamdi Sener is a biophysicist living in Boston. He can be contacted at hamdisener@gmail.com.

Note

1. Even though bacteria are the smallest cells known, compared to the regular cargo molecules they are gigantic structures.

Figure 1. Taken from Wikipedia.org

Figure 2. A) A clathrin coat (or cage) formed by the polymerization of multiple three-legged clathrin molecules. A single clathrin molecule is shown died with cyan. Adapted from RCSB protein data bank website (http://www.rcsb.org/pdb). B) The different stages of receptor-mediated endocytosis. The entire process takes a little less than a minute.

Figure 3. Taken from Wikipedia.org

He has granted you from all that you ask Him. Were you to attempt to count God’s blessings, you could not compute them. But for sure, humankind is much prone to wrongdoing (sins and errors of judgment) and to ingratitude. (Ibrahim 14:34)

Today a large part of modern science focuses on understanding the human body. Researchers working on life sciences hope that one day the secrets of every single detail that make us human will be revealed. Every year billions of dollars are spent by scientific institutions on learning more about us. Actually this fact by itself is enough to suggest how little control we have over things happening in our bodies, and we know even less about the mechanisms of moving, touching, speaking, seeing, or hearing, and so on.

As a scientist, I really cannot guess whether life scientists will ever be able to learn enough to solve the puzzles of the human body, but I feel a lack of satisfaction when the knowledge we have gained from scientific discoveries is compared with what is unknown. In my opinion this is why one of the most intelligent physicists in history, the Nobel laureate Richard Feynman, once said, “I was born not knowing, and have only had a little time to change that here and there” [1]. My understanding is that such a conclusion must be inevitable if the primitive knowledge given to us by modern sciences is not interpreted in the light of a far superior logic that is meant to explain the whole creation. In that sense, I believe that we have to consider every single detail in creation as a vital part of the whole in order not to feel lost before the grand picture of this masterpiece.

Last year, in a seminar at Osaka University Graduate School for Frontier BioSciences, I was thrilled to hear Professor Keichi Namba say, “Japan’s fastest supercomputer dissipates more than billion times the power dissipated by a fly’s brain, yet it is not able to simulate the brain of such a tiny animal.” This worked as a wakening call or a reminder for me to think again about the magnificent arts of the Creator. In particular, I wanted to revise my research on a hearing-related protein from a new perspective, rather than using the mechanical attitude that is followed most of the time.

This article is an attempt to explain an amazing mechanism in our ears that enables us to hear the faintest whispers. A mechanism that is switched off at loud cries to protect us from disturbing noises, yet amplified to make the softest sounds audible. Before starting to explain the basic anatomy of the human ear, I should mention that today the ear’s active amplification mechanism is still being investigated in research centers by biologists and physicists together.

How do we hear? What is happening in the inner ear?

Findings from the last century have shown that our ears are not just simple receivers as we had imagined. In 1979, David Kemp of University College, London discovered that mammalian ears can also emit sound vibrations. By placing a very sensitive microphone close to the eardrum he could detect whistles, implying that there is a source of vibration within the ear [2]. However, before trying to explain the cause of vibrations in the ears, we have to go over the mechanism of hearing briefly: The delicate design of the outer ear, the tympanic membrane (eardrum), and the tiny bones (malleus, incus and stapes) enables to collect sound waves traveling in the medium and transfer them to the inner ear (Figure 1a). In the inner ear the sound waves are sorted according to their frequency and amplitudes and then converted into electrical signals which can be transported to the brain via nerves. At the onset of this process the sound waves are transformed into standing waves on the basilar membrane which is laid along the organ resembling a snail, the cochlea (Figure 1b). The frequency of the incoming sound wave determines the positions of the distortions along the cochlea: High pitches create vibrations at the basal end of the cochlea (i.e. adjacent to the middle ear) whereas low frequencies vibrate closer to the apical end (Figure 1c) where the cochlea gets narrower. This geometry helps our ears to act as a frequency analyzer.

The efferent and afferent nerves that connect the ear to the central nervous system are attached to the organ of Corti, which is situated right next to the basilar membrane, extending over the cochlea. In other words, Corti is the sense organ of hearing, converting the motion of the basilar membrane into electrical signals that are conducted to the brain via neuronal cells [3]. The organ of Corti is also lined with multiple rows of sensory hair cells.

The hair cells of the organ of Corti

Corti is decorated with two different sets of sensory cells: single row of inner hair cells (IHCs) accompanied with 3–4 rows of outer hair cells (OHCs), both spanning the whole cochlear tube (Figure 2a). They are called “hair cells” because both IHCs and OHCs have typical bundles of stereocilia that contain mechanosensitive ion channels (Figure 2b).

The major function of IHCs is to detect the sound waves and then convert them into equivalent electrical signals that are to be interpreted by the brain. When the basilar membrane is perturbed by the incoming sound waves, the IHCs found in that region sense this activity by the movement of their hair bundles (bundles of stereocilia). The hair bundles of IHCs deflect and re-align as the basilar membrane moves up and down (Figure 3). We should note that this is an amazingly sensitive process such that deflections of the stereocilia on the order of a few nanometers (one millionth of a millimeter) can be detected and converted into nerve signals by the IHCs [4].

However, this by itself is not sufficient for hearing; no matter how effective IHCs work, the fluid that fills the cochlear tube is a threat to the sound waves traveling in the inner ear. In 1948, a young astrophysicist named Thomas Gold was the first person who has pointed out that the fluidic nature of the cochlea would dampen the sound vibrations and make them too weak to be detected by IHCs. He has concluded that an inherent vibration amplification mechanism is necessary in order to overcome such a problem [5]. Unfortunately, Gold’s statements were overlooked by the physiologists of his time who had performed their hearing related experiments on dead cochleas.

Gold’s predictions were justified around ten years later by William Rhode, a physiologist from University of Wisconsin, who has shown that the vibrations of the basilar membrane in live tissue samples are stronger than anticipated [6]. In the present day the existence of an amplification mechanism within a live cochlea is a well accepted fact. The only disagreement among scientists is about how the mechanism of the amplification works. Several scientific laboratories have reported different experiments performed on the organ of Corti and they have proposed different models. At the center of one of these models is prestin, a membrane protein which is not found in any cell but OHCs in the human body.

Electro-motile outer hair cells and prestin

In 1985, the distinctive properties of OHCs were first discovered by William Brownell, a University of Geneva neuroscientist, who has shown that these cells can convert electrical signals into motion: A phenomenon called electromotility. Electromotile OHCs can elongate or shrink in response to electrical charge density changes in their membranes. About a decade ago Peter Dallos and co-workers from Northwestern University in Chicago discovered a membrane protein, unique to OHCs, that can respond to electrical signals [3]. The Dallos group coined the name “prestin” for this protein in an analogy with the musical term “presto” (quickly) due to its rapid response to electrical signals. Various kinds of mammalian cells genetically engineered to produce prestin at their membranes displayed the electromotile responses that are very similar to OHCs.

According to Peter Dallos prestin protein works as a tiny machine which is a crucial element for cochlear amplification [7]. His theory is verified by recent studies which show that cochlear sensitivity in mice decreases hundredfold when prestin activity is disrupted by genetic means [8]. As the sound waves reach the inner ear, prestin-driven electromotility enables the OHCs to move like pistons. The piston movement in phase with the basilar membrane motion amplifies the vibrations and makes them stronger for IHC detection (Figure 4a,b). The prestin-driven vibrations were what Thomas Gold proposed and David Kemp had detected so many years ago. However, scientists are still searching and learning new things about this nanometer scale machine. One of the discoveries showed that prestin can adjust itself according to the amplitude of the incoming sound waves: Basically, the amplification is stronger when the sound waves are hard to hear but gets weaker as the volume increases.

Up to this point, we have briefly explained how the amplification mechanism of hearing in mammals works. Unfortunately, even though it took decades of research for scientists to discover and define the active nature of the mammalian ear, this explanation highlights only a minuscule part of the whole picture. That is why we are still incapable of curing most hearing problems. For example, hearing loss due to slightly disturbed hair cells with damaged stereocilia turns out to be chronic (Figure 5). The medical treatments we have to hand are too primitive to mend such delicate structures. Moreover, hearing aids made by today’s technology are not nearly as effective and functional as needed.

On the other hand, the delicacy of the hair cells and the limited control scientists have over them are not the only lessons we have learned from research on the inner ear. We cannot overlook the other messages attached to the research on the grounds that the time given to us is just too short to comprehend. It is an undeniable fact that the sense of hearing is designed in the best way to serve human beings. The different characteristics of hearing amplification at different sound levels make life much easier for us: Prestin-driven hearing is most effective when the sound waves are weak and harder to hear. This way the incoming sound waves are amplified enabling us to hear the faintest whispers. However, as the sound strength increases, the prestin-driven amplification gradually gets weaker and finally diminishes after a point to make sure that loud noises are less disturbing and hazardous for us. In my opinion, this amazing quality of a tiny protein found in our ears is one of the pieces of evidence that remind us of the necessity of pondering the favors of our Creator. Qur’anic verses such as Ibrahim 34 at the beginning of this article give us clues about how to interpret scientific findings that reveal the amazing qualities of our bodily organs. May the Creator of our ears allow us to reflect more on His favors and live accordingly.

Hamdi Sener is a biophysicist living in Boston. He can be contacted at hamdisener@gmail.com.

References

1. Gleick, J., Genius: The Life and Science of Richard Feynman. Reprint ed. 1993: Vintage. 560.
2. Kemp, D.T., The evoked cochlear mechanical response and the auditory microstructure- evidence for a new element in cochlear mechanics. Scand Audiol Suppl., 1979. 9: p. 35–47.
3. Zheng, J., et al., Prestin is the motor protein of cochlear outer hair cells. Nature, 2000. 405(6783): p. 149–55.
4. Robles, L. and M.A. Ruggero, Mechanics of the mammalian cochlea. Physiol Rev., 2001. 81(3): p. 1305–52.
5. Gold, T., Hearing II. The physical basis of the action of the cochlea. Proc. Roy. Soc. B., 1948. 135: p. 492–498.
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“… there is a stable order in the world as well as a well-established connection, constant norms and fundamental laws. In this sense, the world is analogous to a clock or a well-designed machine. Every single wheel, every single screw, every single nail not only has a role in order of a machine and an impact in its final benefit but also positive consequences for all living beings, especially for humans.” (Signs of Miraculousness, Seven Heavens, p. 186)

There is a strong parallel between the general principles to be observed for a healthy social structure in a society and the necessary conditions that enable cells to make up a healthy tissue. The laws prevalent in the universe present amazing parallels since they derive from the same divine source. In order to have healthy development in societies, it is necessary to have healthy connections, reciprocal understanding, and correct information transfer between people. Similarly, having healthy cells, which can be considered as micro-societies, also depends on the cells’ continual use of complex signal connection networks and their maintenance of connections with their environments. In order to maintain a harmonious and healthy life in the cell, there must be dense information transfer (through chemical molecules) at all levels with neighbor cells. Thanks to the connection networks that start at their membranes, cells can recognize warnings coming to them and produce responses. Through such information networks, a continuous connection is established in living organisms, starting from their lowest level mechanisms (i.e. molecules in cells and organelles) to their highest level mechanisms (i.e. organs, systems, organisms, populations, ecosystems), in order to ensure a healthy and harmonious processes of development, reproduction, differentiation and aging. Organized as a tissue (micro-society), one of the most amazing features of cells is the way they behave in accord with the society they live in, rather than acting as individualistic beings. Cells behave in a way to make micro-societies possible. In cytology (study of cells), this feature is known as “contact inhibition” (i.e. maintenance of healthy and harmonious operation and development that is based on connection), and its damage may lead to cancer. Every cell is sensitively programmed to receive all signals, coming from inside and outside, and to manage the proper responses to them. Here, the question arises whether a lack or disorder of connection is caused by pathological conditions in cells or whether the emergence of pathological conditions is caused by connection problems. It is generally assumed that, molecular changes in the cell occur first (i.e. mutation) and then this mutation leads to abnormalities and connection problems at the levels of tissue, organ, and even organism. Damage to communication or connection and disorders in this system are a very important reason for the appearance of some pathological conditions (such as an abnormal increase of cells, cancer and death). Thus, diagnosis and treatment of many diseases today depends on knowledge of how biological communication and connection are harmoniously established.

Cells are designed to control their behavior through special signal molecules that can themselves function as stimulatory. For instance, using signal molecules, cells can establish colonies or biofilms. Moreover, plant cells, through channels known as plasmodesmata, maintain their connection with neighboring cells and trade certain materials. In the state of illness, the density (among cells) of signal molecules that are transferred in the plasmodesmata changes.

Hormones, reproduction factors and neurotransmitters are charged with ensuring transportation and communication at different levels. Cell and tissue elasticity and their adaptability are increased by this diversity in signal operations. Different ways are used to transmit signals into the cell depending upon the characteristics of the signals. For example, hydrophobic (water-avoiding) molecules like steroid hormone pass directly through the cell membrane and connect to their receptors in the cell. The receptors that are responsible for decoding genes stimulate the decoding of related genes. If a problem (mutation) occurs in the molecules that are responsible for transportation and communication, the transportation and communication breaks down and the cancer process is triggered. The existence of continuously reproducing cells in inappropriate times and places is an important symptom of cancer initiation. For example, in colon and rectum cancer, if a mutation occurs on the Ras protein, which is one of the signal proteins that takes the “Reproduce!” message from the cell membrane the cutting off of the GTP molecule, which is responsible for turning the signal molecule on and off, is blocked, and since the molecule stays permanently active a signal like “Reproduce!” is permanently sent inside the cell. Thus, the benefits of the medicines that are used in cancer treatment and that show their effects by hindering signals on the cell membrane level are observed in the non-existence of this mutation on Ras proteins. If the mutation happens the medicines mentioned above cannot be effective. Today, the presence of the mutation can be determined by a biopsy taken from the patient, thus, it has become possible to choose the type of therapy that will be most helpful to that person.

Communication inside the cell can be carried out through ion channels (such as sodium, potassium, and calcium). These channels in membrane behave selectively for every different ion. For example, while voltage-gated channels open and close according to electric charge ligand, (key)-gated (receptor) channels let ions transfer when ligands are tied up. Sodium and potassium ions and the molecular channels that these two passes are responsible for organizing the changes that effect the communication of nerves in the membrane potential. The calcium channel, on the other hand, plays an important role in muscle contraction, and biological incidents like the formation and deformation of bone.

In recent years, the proteins (matrix) that fill the vacancies among cells have been shown to be the main actor in the general control of communication between cells and in the integration of signals coming from their surroundings by hundreds of proofs. It has been pointed out that CCN proteins, which are one of the adaptors, as well as proteins with multiple modules that are responsible for the connection between cell membranes and matrix proteins have a regulatory role at different levels in the control of signal transfers in ion channels, cell differentiation, adherence of cells to each other, cell collapse, programmed cell-death, cartilage formation and the synthesis of new veins. The multi-dimensional and dynamic communication and connections mentioned above related to cells also apply to people. When individuals develop a healthy connection between their inner world and other people, a healthy society emerges. Every individual is granted these potential connection points, which make the existence of an individual possible. The development of a healthy person depends upon activating these connections, organizing them dynamically and keeping them active.

If we place human beings at the center of creation, the first connection that the individuals should make between their Creator and their ego (nafs) is called worship. The ego is both a help and a hindrance to the construction of this connection. The second connection, which is between individuals and their friends, is ensured by good morals, good conduct, and personal virtue. The construction of a healthy social life depends on how many people have good morals, good conduct and virtuous character in a society. If virtue is not accompanied by knowledge, it is highly unlikely that knowledge will raise an individual to a standard of human perfection.

The third essential, the individual’s healthy connection with their surroundings is established through the “ecological dimension of ego,” which is sensitive to the external world. It is very difficult for people whose dimension of ego, which is sensitive to ecological problems and the environment, has not developed to keep the environment clean and take precautions against pollution. The fourth connection that individuals should establish is the connection with their internal world (heart-consciousness, transcendental ego, real self). “O Man! Know yourself first!” and, “The one that knows himself knows his God,” are expressions pointing out the importance of this connection.

For individuals, groups, and societies to have a healthy life as well as to maintain their health at all levels depends on activating these four connections, in other words, establishing coordination and harmony among them and then maintaining this state. When one ignores one of the connections or some of them, or when the coordination between these connections is defective, troubles and illnesses at various levels emerge. Hence, the links that a healthy individual establishes may include those in civil society organizations, and through these further networked and reciprocal communications. Like our cells, which maintain their connection with their environment and neighboring cells via the “contact inhibition” mechanism so that we feel healthy, for people to become healthy at personal and societal level, individuals should actively join civil society organizations and service-centered communities that can enable activation of these four connections and ensure harmony and coordination among them. The Islamic scholar, Bediüzzaman Said Nursi paid special attention to connection in the letters he wrote to his students (the Kastamonu letters) and highlighted it as a point of progress that should be reached:

Since, in today’s world, saving people’s belief for the sake of God is a very important mission that is above everything; since quantity is not very significant compared to quality; since transient and changing political worlds are trivial compared to everlasting, constant, stable services in the name of God-they should not be even compared; they can never be objectives; therefore, we should be satisfied with valuable positions that are granted in the circle of Risale-i Nur. Instead of having extremely well-thoughts about other people or seeing them at high positions superfluously, we need to have extreme loyalty and steadfastness, and utmost connection and sincerity. We should have progress on these points.

Hamza Aydin has a PhD in bio-medicine. He is a freelance writer from Izmir, Turkey.

Life without me is only silence

Every artist wishes to present his work to admiring eyes. In the whole universe, from atoms to star systems, God shows all the details of His art to you, a conscious being; and among His works, He has installed the most splendid ones in your body. He has given you reason and knowledge so that you can easily see and understand them. With knowledge, you can appreciate the meaning and different qualities of existence. However, you need another tool, your five senses, through which you will look at and learn about the material world around you and then turn this knowledge into an appreciation of the meanings behind God’s creation.

If you were not able to perceive light and color (by your eyes), your knowledge of material existence would be insufficient. Similarly, if God had not placed me in your skull, you would not be able to hear and know the songs of birds, the rustling of trees, the babbling of water, or the whistling of wind, which are each a note in the divine musical harmony throughout the universe. Indeed, everything speaks in its own tongue in order to introduce God to people. You use your eyes to perceive the things that speak with the wavelengths of light. You use me to perceive other wavelengths called “sound,” which is caused by the vibration of molecules.

The wavelength of the sounds that I can perceive ranges between 20 and 20,000 Hertz. I am unable to sense frequencies of sound that are above or below those limits. Indeed, it would be better to call this an advantage given by God rather than an “inability.” If the Creator of everything in the universe had not created me with this limited capacity, you would be facing unbearable pain in your head. If He had made me work with a wider range of hearing, you would be disturbed by the footsteps of a little ant, the moaning of an insect laying eggs, the buzzing of beehives, and the sound of the fluttering birds. Therefore, the fact that I have sufficient sensitivity for you to meet your needs is an advantage and an indication of God’s mercy. After all, my Creator gives everybody exactly what they need in a most suitable way and in the best measurements; He never does anything absurd. Do not ever want to have an ear like that of a bat. I am the best one for you.

Do not ever think that my outer, visible part is too simple. My outer ear, which sometimes turns red when you are nervous, is placed in the best position according to the shape of your head so that it can receive sounds in a most efficient way. Because it is made up of elastic cartilage, my outer ear (A) is very flexible, and it won’t break when you lie on it. The curves on me (known as the helix) and the hairs inside my channel are not made without a reason, either. My cartilages have the perfect shape to channel the sound down towards my middle ear according to the intensity of the sound and the direction it comes from. Because this special shape is formed according to the genetic code of a person, it is different in every person. The hairs in the canal serve to protect me from foreign objects like insects or dust. The canal that connects my outer part to my middle part is pretty wide, but if too much fatty wax accumulates here, I might experience temporary hearing loss.

My outer part is followed by my middle ear, which begins with the ear drum (tympanic membrane) (C). Attached to this thin ear drum are three bones: the malleus (D), the incus (E), and the stapes (F), which are all placed in order. These little bones are jointed to each other at an angle of 105 degrees. With an action like a piston, they amplify even the smallest sound vibration coming from the ear drum and transmit it to the middle ear. My middle ear space is connected to your pharynx by a very thin canal called the Eustachian tube (G). In order to protect my ear drum from rupture, I recommend that you open your mouth during an explosion or an intense sound. In that way, the sound waves that enter through your mouth will balance with the sound waves in my canals so that my ear drum is protected.

My inner part, followed by my middle part, is the most vital and sensitive area. Therefore, it is surrounded and protected by the bones of your skull. This inner part, which is an amazing piece of art and technology, comprises two wonderful receptor components. Those two little parts are placed in the same narrow area inside the temporal bone, but they perform different tasks. One of them is the cochlea (H), which is involved with hearing. The other part is the balance (vestibular) canals, which consist of the semicircular canals (I), the saccule (J), and the utricle (K). This balance organ enables you to stand straight and walk, run, or move without bumping or falling.

Like carved marble or forged metal, those parts are crafted out of bones that form a beautiful and intricate whole. My cochlea is divided widthwise by a bony tube. The upper compartment above the tube is connected to an oval window, which is an outlet to the middle ear. The lower compartment below the tube is connected to a round window. My inner part is a labyrinth of fluid-filled tubes. The fluid in the bony labyrinth, between the bone and the membranes, is called perilymph, and the other fluid within the membranous structure is called endolymph.

Situated on the basilar membrane (L) of my cochlea is a very small and special organ that you call the organ of Corti. The organ of Corti contains the hearing cells (or hair cells), the receptors (M) that are sensitive to sound waves, and other supporting cells. Because the length of the cells in the organ of Corti varies, different parts of my cochlea are sensitive to sounds of different wavelengths.

The sound waves travel via the malleus, the incus, and the stapes and through my oval window, agitating the perilymph of my cochlea. After that, the sound waves cause Reissner’s membrane (N) in my cochlea to vibrate, which then results in a wave movement in the endolymph. The wave movement continues along this membrane until it reaches my organ of Corti. The special receptor cells (or hair cells) of the organ of Corti are the ultimate vibration receptors. Their surfaces consist of very small strands (cilia). Those little strands bend and twist when the sound waves are received. Right at this point, a very important event occurs: it is the movement of these strands which converts the mechanical energy (that is produced by the vibrations of the sound waves) into electrical impulses. Those electrical impulses are then sent to your brain via the auditory nerve (nervus cochlearis) of the brain, where they are perceived as “sound.” The same sound waves continue their way to the perilymph and pass into the round window, the section between the middle ear and the inner ear. The round window pushes out to dissipate the sound vibrations in the perilymph and thus lessens their pressure.

The speed of the hearing depends on the speed of the sound that travels through my membrane and little bones. However, once the sound waves begin to pass to your brain as an electrical impulse along the auditory nerve, the hearing process increases its speed. Then your brain immediately interprets and reacts to the sound waves. You are not aware of all these rapid activities which are done perfectly in fractions of a second. You only say that you can hear something ordinarily. Have you ever thought before about how hearing takes place? Do you think you would have a clue about the sounds and music in the universe if God had not created me as your hearing organ?

Think about it, Peter! God knows exactly what you need for your life and equips your body accordingly. If there were no God, would such a complicated organ as your ear form by itself in your skull? Can it be a simple “coincidence” where some biological mechanisms take place successfully and in order without any plan or project and they produce such a splendid organ as me with all my sections? Like every reasonable and thoughtful person, you now understand that I cannot be the result of simple coincidence but only a creation of our God Almighty, don’t you?

Maintaining your balance

So far, what I have told you about is my duty to hear. Now I must also tell you about my duty of balance, so that you can better understand how miraculous I am.

Have you ever seen an acrobat walking on a rope or a mountain climber in action? Or shall I give a better example that might be more familiar to you? Remember what you do on your bicycle to keep from falling off. At the slightest mistake, the acrobat might topple from the rope, the climber might slip off the cliff face, and you might fall off your bicycle. While you are making unconscious (reflex) movements to keep your balance, have you ever thought about what busy operations are going on in my system? I have been equipped with very sensitive receptors which help you stay stable during your continual, different movements. Those receptors immediately recognize the changes occurring as a result of your slightest motion; they warn your body to adjust to your new position by sending out information to the spinal cord and to the brain about the new situation.

You may wonder how these two processes, hearing and balance, can take place in such a small area of the body, the inner ear. It is our Creator, God, who puts microscopic cells in a narrow place and runs the most sensitive and important operations via those little cells.

How do you feel the sensation of balance and how do you react with the right reflex action? To find an answer to that, you need to re-examine my anatomical structures mentioned before. At the base of my semicircular canals is a bulb-like enlargement which opens to the saccule and the utricle. My three semicircular canals are situated at 90-degree angles to each other in three-dimensional space.

My semicircular canals contain few sensory hair cells but there are plenty of them in the bulb-like enlargement. The strands of these cells, which are placed delicately, have enough elasticity to twist and bend during a movement. The receptors for balance in the saccule and the utricle are covered by a thin membrane which contains a gelatinous layer and tiny calcite crystals (cupula terminalis). Depending on its density, the endolymph fluid in my semicircular canals moves against the direction that your head and body move in. Similar to the uncontrolled movement of passengers in an accelerating or moving vehicle, depending on the speed and the direction, the movement and the speed of the endolymph differs from the general movement of your body. For example, when a car turns right, the passengers move to the left with the turning acceleration, and when a fast-moving car brakes suddenly, the passengers are thrown forward. Similarly, depending on its acceleration and momentum, every change in your movement causes the fluid in my semicircular canals to move. Triggered by the movement of the endolymph fluid, the gelatinous mass with the calcite pieces is displaced, causing the strands of the receptors to twist. Every movement of your head warns the cells of different parts, and via the vestibular nerve (nervus vestibularis) the nervous system is notified of changes occurring in your balance.

Thankfulness and contemplation

You have now seen what amazing works my two compartments, the balance and the hearing organs produce. All through your life, the former serves you by maintaining your balance without missing any of your movements, while the latter enables you to learn about the thousands of types of sounds in the world. Once you consider all of your movements in your life, you will see that my two organs perform their duties perfectly without ever getting tired, giving up, or complaining. We do not ask for any fee from you in return for those benefits, either. In fact, when God Almighty created you, placed us in your skull and set up our connection with the related center in your brain, He did not ask for any fee from you. All He wants you to do is to think about those blessings and be thankful to Him.

If you visited a hospital, you might see a lot of scenes which would lead you to think about God’s blessings on you and thank Him. Serious ear illnesses include middle ear infection (otitis media), which is frequently seen in children; otosclerosis, which is the limited ability of the stapes to transmit sound waves because its base becomes fixed to the oval window; and several hearing disorders which might be present at birth or occur later in life, depending on the level of damage to the auditory nerve. Witnessing the effects of those illnesses, you would understand how important it is to be able to hear and stand straight and balanced, and so see how blessed you are. At every step you take, when you are lying down or standing up, or every time you hear the twittering of birds, a nice melody, or the sweet voice of your parents, you will now appreciate the greatness and the mercy of our Lord God Almighty, who has engraved the meanings of all those sounds in your mind.

Peter! Until now, you have used me to listen to others, but today it was my turn to be listened to while I told you about myself. However, I must admit that I have only been able to explain to you the details of about one-hundredth of the beauties displayed in me and my delicate anatomical structure. If I attempted to present you with all the details about me discovered by developing technology and science and the meanings attached to them, there would not be enough pages in the magazine that you are holding now. Indeed, you do not need that much information either. My main aim here is to draw your attention to me, and thus let you know our God and bring you closer to Him. I hope I am successful in that. From now on, you will hear my ringing occasionally and remember me so that you will be saved from your heedlessness once again.

Irfan Yilmaz is a professor of biology at Dokuz Eylul University, Izmir, Turkey.

In May 2003, Roderick Mackinnon’s research group at Rockefeller University has published the three-dimensional atomic structure of a voltage-gated potassium channel. MacKinnon also received the Nobel Prize in 2003 for the first potassium channel structure

How electrical signals are conducted through nerve cells has been understood with some detail in the last fifty years, after the seminal work of Hodgkin and Huxley, which earned them a Nobel Prize in 1963. After 40 years, another study is appreciated in the scientific community as the end of one era and the beginning of another one.

Cells, body’s building blocks, are bound by membranes that are impermeable to ions, atoms that carry positive or negative charge. Nerve cells are specialized for having very long arms that can carry electric potentials on their membranes for very long distances. The electric potential (voltage difference) is the result of unequal number of charges across the inside and outside of the cell membrane. Hodgkin and Huxley explained the movement of the electric potential on the membranes by the selective opening of ion channels, proteins embedded in membranes to allow the passage of certain ions. As channels are opened in one part of the nerve cell to allow an electrical potential change, the neighboring stretches somehow sense the change in voltage and open their channels as well. The propagation of the electric potential depends on the fast sensing, opening and closing of these channels. The molecular details of these voltage-gated channels have been somewhat obscure; however important properties have been determined using methods pioneered by Hodgkin and Huxley, generally dubbed electrophysiology, the study of biological material using electrical methods. Scientists

have imagined channel proteins as many helices running through the membrane, some of which could be pulled to the inside or outside of the cell depending on the voltage across the

membrane. Movement of these helices across the membrane could open channels for potassium or sodium. Finally in May 2003, Roderick Mackinnon’s research group at Rockefeller University has published the three-dimensional atomic structure of a voltage-gated potassium channel. MacKinnon also received the Nobel Prize in 2003 for the first potassium channel structure, which explained the selectivity of a potassium channel for allowing only potassium ions to pass, but nothing else.

MacKinnon is a mixed structural biologist and electrophysiologist. His group has isolated potassium channel molecules from membranes, and tested them for strict functionality as it has been observed that protein molecules isolated out of their natural environments may lose their activities and chemical properties. The next step of their study was to crystallize the channel molecules-much like forming salt crystals-and diffract x-rays through the aligned molecules in the lattice of their crystals. These diffraction patterns are mathematically solved to give atomic positions of electrons, hence atoms, in the protein crystal. Several research groups failed at this step, since purified potassium channels never formed crystals, as flexible protein molecules are unlikely to form crystals. Here, MacKinnon cleverly used antibodies they developed specifically against the channel. These antibodies, used radically differently than they are in nature, overcame the flexibility of the voltage-sensing regions of the channel, by binding to the channel and fixing it to a specific conformation. The ordered channel crystallized and gave the structure of the potassium channel and the antibody bound to it.

The structure of the channel consists mostly of helices, which in the center surround a potassium-conduction pore, and “voltage-sensing paddles” in the periphery. When the gate is closed, the helical paddles lay parallel at the cellular side of the membrane. Gate opening only happens when the paddles are pulled through the membrane to the outer side as voltage pulls the positive charge of the paddles to the outside (see figure). Now, it looks like 50 years of data collected by electrophysiologists and biochemists can be explained coherently (such as the observed 14 positive charges residing on the paddles moving through the membrane). As is usual with such discoveries, many new questions are asked, such as how the charged paddles can go through the oily, highly uncharged membranes. There are also valid scientific objections, such as the antibody distorting the potassium channel structure. However, this is one of those bright moments in any field of research, when researchers go over the threshold of collection of enough observations to discovery and understanding.

References

• Jiang, Y., Lee, A., Chen, J., Ruta, V., Cadene, M., Chait, B.T., MacKinnon, R., Nature 423, 33-41 (2003).
• Jiang, Y., Ruta, V., Chen, J., Lee, A., MacKinnon, R., Nature 423, 42-48 (2003).
• Sigworth, F.J., Nature 423, 21-22 (2003).