The VGL-Chanome: A Protein Superfamily Specialized for Electrical Signaling and Ionic Homeostasis

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Science's STKE  05 Oct 2004:
Vol. 2004, Issue 253, pp. re15
DOI: 10.1126/stke.2532004re15

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Complex multicellular organisms require rapid and accurate transmission of information among cells and tissues and tight coordination of distant functions. Electrical signals and the resulting brief changes in intracellular calcium, in vertebrates, control contraction of muscle, secretion of hormones, sensation of the environment, processing of information in the brain, and output from the brain to peripheral tissues. In nonexcitable cells, transient changes in intracellular calcium signal many key cellular events, including secretion, gene expression, and cell division. In epithelial cells, huge ion fluxes are conducted across tissue boundaries. All of these physiological processes are mediated in part by members of the voltage-gated ion channel protein superfamily, which constitutes one of the largest groups of signal transduction proteins, ranking third after the G protein–coupled receptors and the protein kinases. Each member of this superfamily contains a similar pore structure, usually covalently attached to regulatory domains that respond to changes in membrane voltage, intracellular signaling molecules, or both. Eight families are included in this protein superfamily—voltage-gated sodium, calcium, and potassium channels; calcium-activated potassium channels; cyclic nucleotide–modulated ion channels; transient receptor potential (TRP) channels; inwardly rectifying potassium channels; and two-pore potassium channels. This STKE Review, with six figures, one table, 233 citations, and three supplemental tables, identifies all of the members of this protein superfamily in the human genome, reviews the molecular and evolutionary relations among these ion channels, and describes their functional roles in cell physiology.