Voltage-gated ion channel

Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical membrane potential near the channel; these types of ion channels are especially critical in excitable cells such as neurons.

They have a crucial role in excitable neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are ion-specific, as channels specific to Na+, K+, Ca2+, and Cl- ions have been identified.[1] In either case, the opening and closing of the channels are triggered by changing ion concentration on either side of the cell membrane.[2]

Structure

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. The functionality of voltage-gated ion channels is attributed to its three main discrete units: the voltage sensor, the pore or conducting pathway, and the gate.[3]

Examples include:

Mechanism

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 difference is introduced over the membrane, the associated electric field induces 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 electric 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.[4] It has many positive charges such that a high positive charge outside the cell repels the helix, keeping the channel in its closed state. Depolarization of the cell interior causes the helix to move, inducing a conformational change such that ions may flow through the channel (the open state). Potassium channels function in a similar way, with the exception that they are composed of four separate polypeptide chains, each comprising one domain.

The voltage-sensitive protein domain of 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. A similar voltage sensor paddle has also been found in a family of voltage sensitive phosphatases in various species.[5] Genetic engineering of the paddle region from a species of volcano-dwelling archaebacteria into rat brain potassium channels results in a fully functional ion channel, as long as the whole intact paddle is replaced.[6] 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.[7]

Although voltage-gated ion channels are typically activated by membrane depolarization, some channels, such as inward-rectifier potassium ion channels, are activated instead by hyperpolarization.

References

  1. ↑ Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Voltage-Gated Ion Channels.
  2. ↑ Catterall, William A. (2000-04-01). "From Ionic Currents to Molecular Mechanisms". Neuron 26 (1): 13–25. doi:10.1016/S0896-6273(00)81133-2. ISSN 0896-6273. PMID 10798388.
  3. ↑ Bezanilla, Francisco (2005-03-01). "Voltage-gated ion channels". IEEE transactions on nanobioscience 4 (1): 34–48. ISSN 1536-1241. PMID 15816170.
  4. ↑ Voltage sensor in the voltage gated sodium and potassium channels | PharmaXChange.info
  5. ↑ Murata, Y.; Iwasaki, H.; Sasaki, M.; Inaba, K.; Okamura, Y. (2005). "Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor". Nature 435 (7046): 1239–1243. doi:10.1038/nature03650. PMID 15902207.
  6. ↑ Alabi AA, Bahamonde MI, Jung HJ, Kim JI, Swartz KJ (November 2007). "Portability of paddle motif function and pharmacology in voltage sensors". Nature 450 (7168): 370–5. doi:10.1038/nature06266. PMC 2709416. PMID 18004375.
  7. ↑ Long SB, Tao X, Campbell EB, MacKinnon R (November 2007). "Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment". Nature 450 (7168): 376–82. doi:10.1038/nature06265. PMID 18004376.

See also

External links

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