Cardiac sarcolemmal K_ATP channels: Latest twists in a questing tale!

Reconstitution of K_ATP channel activity from coexpression of members of the pore-forming inward rectifier gene family (Kir6.1, KCNJ8, and Kir6.2 KCNJ11) with sulfonylurea receptors (SUR1, ABCC8, and SUR2, ABCC9) of the ABCC protein sub-family, has led to the elucidation of many details of channel gating and pore properties, as well as the essential roles of Kir6.2 and SUR2 subunits in generating cardiac ventricular K_ATP. However, despite this extensive body of knowledge, there remain significant holes in our understanding of the physiological role of the cardiac K_ATP channel, and surprising new findings keep emerging. Recent findings from genetically modified animals include the apparent insensitivity of cardiac sarcolemmal channels to nucleotide levels, and unenvisioned complexities of the subunit make-up of the cardiac channels. This topical review focuses on these new findings and considers their implications.