Intracellular regulation of inward rectifier K+ channels

Inward rectifier potassium (Kir) channels comprise a relatively young gene family of ion channels whose first member was isolated in 1993. A common pr operty its members share is a strong dependence on intracellular regulators such as polyamines, nucleotides, phospholipids, kinases, pH and guanosine- triphosphate binding proteins (G-proteins). The physiological role of Kir c hannels is to modulate the excitability and secretion of potassium (K+) to maintain K+ homeostasis, under the control of various intracellular second messengers. Structurally, Kir channels are assembled from four alpha-subuni ts each carrying the prototypic K+-channel pore region lined by two transme mbrane segments with intracellular N- and C-termini. The exact molecular me chanism of Kir channel gating by intracellular second messengers is of cons iderable biophysical interest. Recent studies have gained significant insig ht into the molecular mechanism of intracellular regulation by pH. This rev iew illustrates the various modes of regulation of this class of ion channe l and the present knowledge of the underlying molecular mechanisms.