- Voltage-gated ion channel
Voltage-gated ion channels are a class of transmembrane
ion channels that are activated by changes in electrical potential differencenear the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells.
They have a crucial role in excitable neuronal and muscle tissues, allowing a rapid and co-ordinated depolarisation in response to triggering voltage change. Found along the
axonand at the synapse, voltage-gated ion channels directionally propagate electrical signals.
They generally are composed of several subunits arranged in such a way that there is a central pore through which ions can travel down their
electrochemical gradients. The channels tend to be ion-specific, although similarly sized and charged ions may sometimes travel through them.
From crystallographic structural studies of a
potassium channel, assuming that this structure remains intact in the corresponding plasma membrane, it is possible to surmise that when a potential differenceis introduced over the membrane, the associated electromagnetic fieldinduces a conformational change in the potassium channel. The conformational change distorts the shape of the channel proteins sufficiently such that the cavity, or channel, opens to admit ion influx or efflux to occur across the membrane, down its electrochemical gradient. This subsequently generates an electrical current sufficient to depolarise the cell membrane.
Voltage-gated sodium channels and calcium channels are made up of a single polypeptide with four homologous domains. Each domain contains 6 membrane spanning alpha helices. One of these helices, S4, is the voltage sensing helix. It has many positive charges such that a high positive charge outside the cell repels the helix - inducing a conformational change such that ions may flow through the channel. Potassium channels function in a similar way, with the exception that they are composed of four separate polypeptide chains, each comprising one domain.
protein domainof these channels (the "voltage sensor") generally contains a region composed of S3b and S4 helices, known as the "paddle" due to its shape, which appears to be a conserved sequence, interchangeable across a wide variety of cells and species. Genetic engineeringof the paddle region from a species of volcano-dwelling archaebacteriainto rat brain potassium channels results in a fully functional ion channel, as long as the whole intact paddle is replaced. [Alabi AA, Bahamonde MI, Jung HJ, Kim JI, Swartz KJ. "Portability of Paddle Motif Function and Pharmacology in Voltage Sensors." "Nature", November 15, 2007. ] This " modularity" allows use of simple and inexpensive model systems to study the function of this region, its role in disease, and pharmaceutical control of its behavior rather than being limited to poorly characterized, expensive, and/or difficult to study preparations. [Long SB, Tao X, Campbell EB, MacKinnon R. "Atomic Structure of a Kv Channel in a Lipid Membrane-Like Environment." "Nature", November 15, 2007.]
* [http://www.iuphar-db.org/index_ic.jsp The IUPHAR Compendium of Voltage-gated Ion Channels 2005]
Voltage-dependent calcium channel
Sodium ion channel
Voltage-gated potassium channel
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