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SYMPOSIUM REVIEW: Gating of two pore domain potassium channels
Author(s) -
Mathie Alistair,
AlMoubarak Ehab,
Veale Emma L.
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.192344
Subject(s) - gating , biophysics , potassium channel , chemistry , intracellular , ion channel , kcsa potassium channel , membrane potential , extracellular , cooperativity , ligand gated ion channel , voltage gated ion channel , inward rectifier potassium ion channel , biochemistry , biology , receptor
Two‐pore‐domain potassium (K2P) channels are responsible for background leak currents which regulate the membrane potential and excitability of many cell types. Their activity is modulated by a variety of chemical and physical stimuli which act to increase or decrease the open probability of individual K2P channels. Crystallographic data and homology modelling suggest that all K + channels possess a highly conserved structure for ion selectivity and gating mechanisms. Like other K + channels, K2P channels are thought to have two primary conserved gating mechanisms: an inactivation (or C‐type) gate at the selectivity filter close to the extracellular side of the channel and an activation gate at the intracellular entrance to the channel involving key, identified, hinge glycine residues. Zinc and hydrogen ions regulate Drosophila KCNK0 and mammalian TASK channels, respectively, by interacting with the inactivation gate of these channels. In contrast, the voltage dependence of TASK3 channels is mediated through its activation gate. For KCNK0 it has been shown that the gates display positive cooperativity. It is of much interest to determine whether other K2P regulatory compounds interact with either the activation gate or the inactivation gate to alter channel activity or, indeed, whether additional regulatory gating pathways exist.