Sarcolemmal K_ATP channels: What do we really know?

K_ATP channels are present at an extremely high density in the heart, and we know from in vitro studies that channel activation causes dramatic action potential shortening and contractile failure. But, if and when this happens in vivo is still a matter of debate. Twenty one years of intense study have led to a well-developed understanding of the molecular basis of K _ATP channel activity. Structure-function studies, together with cellular experiments probing regulatory molecules have told us much about the way the K_ATP channel can activate, and gene-targeting and proteomic tools have further elucidated determinants of in vivo function. However, the true physiological determinants of sarcolemmal K_ATP activity remain elusive, we still await full illumination of the role of the channel in the intact heart.