Inwardly rectifying K  (Kir) currents were first identified in skeletal muscle. Under physiological conditions, Kir channels generate a large K  conductance at potentials negative to EK but permit less current flow at potentials positive to EK. Kir channels have been found in a wide variety of cells: cardiac myocytes, neurons, blood cells, osteoclasts, endothelial cells, glial cells, epithelial cells, and oocytes. G protein-gated K  (KG) channels, which are activated via pertussis toxin (PTX)-sensitive G proteins, also show inward rectification. In addition, ATP-sensitive K  (KATP) channels, which were originally defined as being opened by a decrease in intracellular ATP (ATPi) also belong to the Kir channel family. Accordingly, Kir channels not only orchestrate the passive and active electrical properties of cells, but they are also involved in G protein-coupled receptor (GPCR) signaling, and they may link cellular metabolic state and membrane excitability in vivo. Kir channel structures possessed a common motif of two putative membrane-spanning domains (TM1 and TM2) linked by an extracellular pore-forming region (H5) and cytoplasmic amino (NH2)- and carboxy (COOH)-terminal domains.
The H5 region serves as the “ion-selectivity filter” that shares with other K -selective ion channels the signature sequence T-X-G-Y(F)-G. Kir channel structures lack the S4 voltage sensor region that is conserved in voltage-gated Na , Ca2 , and K  channels. The functions of Kir channels can be regulated by small substances (top panel) and by proteins (bottom panels). The small substances are ions such as H , Mg2 , and Na ; polyamines; phosphorylation; and membrane-bound phospholipids. Protein-protein interaction involves sulfonylurea receptors (SUR), G proteins liberated from G proteincoupled receptors (GPCR), and anchoring proteins. The localization of Kir channels on a cell may determine their particular function. The channels may be distributed homogeneously in nonpolarized cells or in a specific pattern in membranes of polarized cells such as epithelia and neurons. Specific localization patterns play a role in unidirectional transport of K  and in the organization of signal transduction. Particular channels and other transport mechanism may be gathered in microdomains such as detergent-resistant membrane microdomains (DRMs) and caveolae. Such colocalization may be necessary for the physiological coupling of iontransport mechanisms.

References

1.Hibino H,et al. Physiol Rev. 2010;90(1):291–366.