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

J Physiol. 2004 Jan 15;554(Pt 2):285-94. doi: 10.1113/jphysiol.2003.048439. Epub 2003 Aug 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • GTP-Binding Proteins / physiology*
  • Guanosine Triphosphate / pharmacology
  • Guanosine Triphosphate / physiology
  • Humans
  • Potassium Channels, Inwardly Rectifying / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / physiology


  • Potassium Channels, Inwardly Rectifying
  • Guanosine Triphosphate
  • GTP-Binding Proteins