G-protein mediated gating of inward-rectifier K+ channels

G-protein regulated inward-rectifier potassium channels (GIRK) an part of a superfamily of inward-rectifier K+ channels which includes seven family me mbers. To date four GIRK subunits. designated GIRK1-4 (also designated K(ir )3.1-4), have been identified in mammals, and GIRK5 has been found in Xenop us oocytes. GIRK channels exist in vivo both as homotetramers and heterotet ramers. In contrast to the other mammalian GIRK family members, GIRK1 can n ot form functional channels by itself and has to assemble with GIRK2, 3 or 4. As the name implies, GIRK channels an modulated by G-proteins; they are also modulated by phosphatidylinositol 4,5-bisphosphate, intracellular sodi um, ethanol and mechanical stretch. Recently a family of GTPase activating proteins known as regulators of G-protein signaling were shown to be the mi ssing link for the fast deactivation kinetics of GIRK channels in native ce lls, which contrast with the slow kinetics observed in heterologously expre ssed channels. GIRK1, 2 and 3 are highly abundant in brain, while GIRK4 has limited distribution. Here, GIRK1/2. seems to be the predominant heterotet ramer. In general, neuronal GIRK channels an involved in the regulation of the excitability of neurons and may contribute to the resting potential. In terestingly, only the GIRK1 and 4 subunits are distributed in the atrial an d sinoatrial node cells of the heart and are involved in the regulation of cardiac rate. Our main objective of this review is to assess the current un derstanding of the G-protein modulation of GIRK channels and their physiolo gical importance in mammals.