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Neuronal two‐pore‐domain potassium channels and their regulation by G protein‐coupled receptors
Author(s) -
Mathie Alistair
Publication year - 2007
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.2006.121582
Subject(s) - phosphatase , potassium channel , microbiology and biotechnology , g protein , inward rectifier potassium ion channel , g protein coupled inwardly rectifying potassium channel , g protein coupled receptor , chemistry , biophysics , receptor , ion channel , ligand gated ion channel , gq alpha subunit , biology , biochemistry , phosphorylation
Leak potassium currents in the nervous system are often carried through two‐pore‐domain potassium (K2P) channels. These channels are regulated by a number of different G protein‐coupled receptor (GPCR) pathways. The TASK subfamily of K2P channels are inhibited following activation of the G protein Gα q . The mechanism(s) that transduce this inhibition have yet to be established but there is evidence to support a role of phosphatidylinositol 4,5‐bisphosphate (PIP 2 ) hydrolysis products, depletion of PIP 2 itself from the membrane, or a direct action of activated Gα q on TASK channels. It seems possible that more than one pathway may act in parallel to transduce inhibition. By contrast, TRESK channels are stimulated following activation of Gα q . This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity. TREK channels are the most widely regulated of the K2P channel subfamilies being inhibited following activation of Gα q and Gα s but enhanced following activation of Gα i . The multiple pathways activated and the apparent promiscuous coupling of at least some K2P channel types to different G protein regulatory pathways suggests that the excitability of neurons that express K2P channels will be profoundly sensitive to variations in GPCR activity.