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 property 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 channels 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-subunits each carrying the prototypic K+-channel pore region lined by two transmembrane segments with intracellular N- and C-termini. The exact molecular mechanism of Kir channel gating by intracellular second messengers is of considerable biophysical interest. Recent studies have gained significant insight into the molecular mechanism of intracellular regulation by pH. This review illustrates the various modes of regulation of this class of ion channel and the present knowledge of the underlying molecular mechanisms.