The ion channels for the keyhole

The cell membrane is a thin layer of lipids, isolated from the outside world in the cell. It maintains the cellular components of crucial importance, it prevents the exchange of soluble molecules. More transport equipment (such as proteins and other) in the cell membrane, and thus communicate with the extra cellular environment. Ion channels in these devices. This membrane forms a physical barrier to cells and allows the components of the cell environment is strictly regulated, so that the ideal conditions for cell metabolism. Membrane, but it also means that as the movement of substances in and out of the pores of the specialized cells are needed. This forms a channel through the membrane is salt (charged atoms and ions) and large molecules such as sugar.

Most of these channels are selective for certain membrane materials and can be opened and closed, and electric garage door remote control or cell keys with chemicals known as ligand.

Some of these channels as a membrane pump, fuel energy in some chemical or other objects. The most studied is the "sodium-potassium ATPase, rather than the revolving door in the membrane and simultaneously spit the plane return to the sodium-potassium. Uvrtiti increase pump 3 sodium ions for potassium ions 2, pulling in the sense that over time, the cells built in the net negative charge in relation to the environment "extra cellular" fluid.

Nerve Cells (Neurons) that this situation is to give information to one hundred and twenty meters per second. This is achieved by ion channels in the cell membrane open at a fraction of a second to a small number of positively charged ions flow of sodium in nerve cells with a loss of nerves called the action potential activity. This action potential travels along the Neuron, and sometimes to the strengthening of other ion channels, which are characterized by electrical activity. Plan nerve and the frequency of action, information very quickly from one body to another.

But what if you have a PIN? How this type of crime? The solution is simple elegance. If the PIN code of the skin, pain perception is determined by the production of action potentials of pressure, nerve fibers in the dermis. Membrane of nerve fibers offer open ion channels permeable to sodium ions postively charged.

The entry of sodium content activated cells, action potentials, nerve fibers in the spinal cord. In spinal cord, signals to other groups of nerve cells that connect with the parts of the brain that provides pain. Information is also transmitted to other nerve cells, muscle groups, leaving the feet. The result is that because of the activity of ion channels, leave PIN Ostrog almost as soon as you feel.

But ion channels is not only to work on the nervous system. Indeed, life can not be first, without family ion channels in action around the time of conception, so that when the sperm fuses with the egg, the electrical properties of the membrane of the egg must be changed to prevent further dissemination of the sperm.

Ion channels also that the pacemaker keeps pace. Each pulse of the movement of calcium ions in myocardial cells through calcium channels. This leads to a rapid release of calcium stores in cells even more (of the second type of calcium channel), which is the heart muscle to beat. Each cell is a type of ion channel instrument to carry out their physiological functions.

Forecasts, given the important role you play in the ion channels in our bodies, many human diseases are caused by the ion channels that does not work. In some cases it is caused by mutations or changes in the genes coding for proteins to ion channels. About a similar problem may occur if the ion channels are proteins in their function is not working. Cystic fibrosis, epilepsy and certain heart rhythm disturbances (arrhythmias), such as "Long KT syndrome are examples of this phenomenon.

There is nothing about genetics, but because of food poisoning bacteria, including the vulnerability of ion channel function by producing toxins that cause diarrhea can be defined by each of the ion channels in cells podstava sets.

All these factors mean that ion channels, especially for therapeutic drugs, for example, during the operation targeted areas of anesthesia and nerve-muscle-blockers in the treatment of neurological and psychiatric disorders, such as' epilepsy and schizophrenia, CARDIAC ion channel drugs that block the heart rate. Surprisingly, most of the substances used are based on random discoveries - something, if we only use the system later. But now we are in a time of "rational" and pharmacologically similar suit measurement is the recipient of the mind.

The idea of ion channels: A little history

Does "ion channels" built in 1950 by the pioneering work of Alan Hodgkin and Andrew Huksley in Cambridge, and Bernard Katz at University College London. It is shown that the movement of sodium and potassium ions, force the action potential in nerve cells, working with the Hodgkin-Huksley a Nobel Prize in 1963. Further work in the1960s and 1970 in various laboratories around the world, leading to the identification of the first ion channel protein: The acetylcholine receptor of electric ray (Torpedo califormica).

Until the early 1970s was not NOK evidence to change, the move is a very minor (some picoamperes, which deals with 1/100-billionth that protječe bulb for desk lamp) must move through each channel. But the "noise" in the methods used in the time it was too big for that electricity sićuušni directly measured.

This change is in the mid-1970s, when German scientists Eruin Neher and Bert Sakmann have managed to measure the flow of ions through various channels with the new techniques are developed. Name "Patch bite", this method is that everywhere in the world, and researchers can use the introduction of ions through the channel and the individual in real time. In recognition of their contribution, the Nobel Prize in Medicine in 1991.

More recent advances in molecular genetics have allowed the cloning of various channels and ion channel properties in the protein sequence, which has been built. Another important breakthrough in 1998, when Roderick MacKinnon who Houard Hughes Medical Institute in the U.S., X-ray crystallography to solve the atomic structure of ion channel - in the bacterial potassium channel KcsA from Streptomyces lividans. Mackinnon was awarded the prize for chemistry in 2003.

But what is the structure of an ion channel?

Ion channel protein molecules symmetrical shrinkage of a water-filled cell membranes: kalijevog crystal structure of the KcsA channel from Streptomyces lividans. Cavities, the bridges in the cell. In some aspects of ion channels can be considered as "excitable molecules, such as a feeling.

Various ion channels so that different sensors to different situations, and therefore different mechanisms for each sensor. Some of them involve changes in membrane potential and is known as voltage-gated ion channels. Other small response to chemical (ligand) that Sveže to certain areas of the protein, called ligand-gated ion channels. Channels, the deformations and stresses in the membrane, such as PIN-link or listen to music is mechanosensors.

Channels or activation response, regardless of the offer, and is used as a time window in a series of molecular movements or changes in the conformation of the protein that opens the pores in the skin. Surprisingly, the ion channels can choose between the ion channels that Wednesday passage may form chloride ions, sodium, while the other. This house is without pores, certain types of ions through the very high rates (up to 106 ions per second), while other flows Kochi. On the basis of selective permeability, such as ion channels kalijev channels, calcium channels, sodium channels and so on.

Study of ion channels in action after another

On the question of ion channels that are open today. What is the molecular motions in the ion channel protein that lead to open the pores and the flow of ions through it? Because the classical biochemical method to measure the average activity of thousands of channels, it is not possible to measure the heterogeneity of the dynamics of movements, in May, which will be the most important aspects of their behavior. To answer this question, you should be able to predict the behavior of ion channels one by one. It is so far only a single channel time clamping recordings. But the test that the transitions between open and closed position, they will not be able to probe structural changes in proteins, which form the basis of the mechanisms for opening and closing. Crystal structures also detailed information about the structure of proteins, but only one of many snapshots of the chain configuration can be taken.

Recent advances in the techniques of fluorescence optical, it is possible to directly observe single molecules (eg ion channels) in action. For opening a new era in biotechnology as a "single molecule nano-Biosciences. An extensive internal reject fluorescence micro copy: Total internal reflection occurs when light rays of the thickness of the media as glass, the interface with less density as water (or cells) in the angle is greater than the critical angle. the light is reflected, but part of the light energy distributed in very small distance the less dense media to generate so-called volatile golf. This is then used to excite the fluorescent display molecules. Given the intensity and resolution of the instability in the area exponentially with distance, only a few nano meters through l sample, it is possible that some molecules. images were videotaped in real time along with a special camera (intensified CCD-camera). This technique is completely reject internal fluorescence (or TIRF) Microscopy, by Daniel Akselrod, University of Michigan in the early 1980's.

Based on the visual appearance of internal complete rejection, this technique allows us to predict the behavior of molecules in real time, and in vitro in living cells. Neon display molecules have been studied, but progress in this area is now possible to almost all fluorescently label biomolecules (including ion channels).

The biggest advantage over any conventional TIRF fluorescence microscope using a special type rasvjete known as reduction of the wave of the lighting comes from the small proportion (around one hundred nano meters) in the sample ad, the cone cells alive. Fluorescence in other parts of the sample (who are not interested in) are rejected, so that the detection of molecules. TIRF Microscopy besprimjernom already understand many cellular processes such as protein folding, enzyme catalysis and protein motors move. Well, many laboratories around the world use technology to ion channels in action.

This is a start, but the procedure is safe, a new light on the activities of membrane minijaturnih devices. And researchers see the same path in the action and simultaneously measuring the ionic current through, this technology promises a new era in ion channel idea!