ATP-sensitive K+-channels (KATP) provide a unique link between cell metabolism and excitability in multiple organs and cell types. In smooth muscle, for instance, activation of KATP channels causes vasodilation. In the pancreatic β-cell, they play an essential role in coupling membrane excitability with glucose-stimulated insulin secretion (GSIS). Sulfonylureas, hypoglycemic agents used in the treatment of type 2 diabetes, act by binding to the regulatory SUR1 subunit and inhibiting KATP current, leading to depolarization, Ca2+ entry and insulin secretion. By contrast, KATP-specific channel openers, diazoxide and pinacidil, suppress insulin release and cause lowering of blood pressure, by activating KATP and preventing depolarization-dependent rise in [Ca 2+]i. In the heart, activation of KATP causes action potential shortening in ischemia, and underlies a cardioprotective effect by reducing Ca2+ entry. Over the last few years, significant advances have been made in understanding the molecular basis of channel activity and the role of these channels in physiology and diseases. This mini-review will highlight these advances and point out challenges that will face the next phase of understanding.
|Number of pages||10|
|State||Published - Dec 18 2006|