Gating Mechanism of K_ATP Channels : Function Fits Form

Based initially on their prominence in the squid giant axon, their useful pharmacology, and subsequently on being the first cloned K channels, voltage-gated K (Kv) channels have received the lion's share of attention to their biophysical properties. Kv and Ca-activated K channel kinetics and gating mechanisms have been analyzed, and modeled, in exquisite detail (Hille, 2001). Inward rectifier K (Kir) channels have received less attention, and perusal of the literature indicates that there is still no common understanding of kinetic mechanisms in Kir channels. It is our contention, however, that one is in reach. Amongst Kir channels, ATP-sensitive (K_ATP) channels are uniquely regulated by cytoplasmic nucleotides and specific pharmacological agents. As such, they play a critical role in coupling cellular metabolism to electrical activity, and are major drug targets in pancreatic, vascular smooth muscle and cardiac muscle (Ashcroft, 1988;...