Channelpedia

PubMed 12923211


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir3.2 , Slo1



Title: Cell signal control of the G protein-gated potassium channel and its subcellular localization.

Authors: Yoshihisa Kurachi, Masaru Ishii

Journal, date & volume: J. Physiol. (Lond.), 2004 Jan 15 , 554, 285-94

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12923211


Abstract
G protein-gated inward rectifier K(+) (K(G)) channels are directly activated by the betagamma subunits released from pertussis toxin-sensitive G proteins, and contribute to neurotransmitter-induced deceleration of heart beat, formation of slow inhibitory postsynaptic potentials in neurones and inhibition of hormone release in endocrine cells. The physiological roles of K(G) channels are critically determined by mechanisms which regulate their activity and their subcellular localization. K(G) channels are tetramers of inward rectifier K(+) (Kir) channel subunits, Kir3.x. The combination of Kir3.x subunits in each K(G) channel varies among tissues and cell types. Each subunit of the channel possesses one Gbetagamma binding site. The binding of Gbetagamma increases the number of functional K(G) channels via a mechanism that can be described by the Monod-Wyman-Changeux allosteric model. During voltage pulses K(G) channel current alters time dependently. The K(G) current exhibits inward rectification due to blockade of outward-going current by intracellular Mg(2+) and polyamines. Upon repolarization, this blockade is relieved practically instantaneously and then the current slowly increases further. This slow current alteration is called 'relaxation'. Relaxation is caused by the voltage-dependent behaviour of regulators of G protein signalling (RGS proteins), which accelerate intrinsic GTP hydrolysis mediated by the Galpha subunit. Thus, the relaxation behaviour of K(G) channels reflects the time course with which the G protein cycle is altered by RGS protein activity at each membrane potential. Subcellular localization of K(G) channels is controlled by several distinct mechanisms, some of which have been recently clarified. The neuronal K(G) channel, which contains Kir3.2c, is localized in the postsynaptic density (PSD) of various neurones including dopaminergic neurones in substantia nigra. Its localization at PSD may be controlled by PDZ domain-containing anchoring proteins. The K(G) channel in thyrotrophs is localized exclusively on secretary vesicles, which upon stimulation are rapidly inserted into the plasma membrane and causes hyperpolarization of the cell. This mechanism indicates a novel negative feedback regulation of exocytosis. In conclusion, K(G) channels are under the control of a variety of signalling molecules which regulate channel activity, subcellular localization and thus their physiological roles in myocytes, neurones and endocrine cells.