Evidence for presence of ATP-sensitive K+ channels in rat colonic smooth muscle cells

Abstract

Coexpression of sulfonylurea receptor (SUR) and inward-rectifying K+ channel (Kir6.1 or 6.2) subunit yields ATP-sensitive K+ (KATP) channels. Three subtypes of SUR have been cloned: pancreatic (SUR1), cardiac (SUR2A), and vascular smooth muscle (SUR2B). The distinct responses to K+ channel openers (KCOs) produced in different tissues may depend on the SUR isoform of KATP channel. Therefore, we investigated the effects of pinacidil and diazoxide, two KCOs, on KATP currents in intestinal smooth muscle cells of the rat colon (circular layer) using whole-cell voltage clamp. Pinacidil stimulated a time-independent K+ current evoked by various test potentials from a holding potential of -70 mV. The reversal potential of the stimulated current was about -75 mV, which is close to the equilibrium potential for K+ (EK). Both pinacidil and diazoxide dose-dependently stimulated K+ currents (evoked by ramp pulses), with EC50 values of 1.3 and 34.2 µM, respectively. The stimulated current was completely reversed by glybenclamide (3 µM). Since the EC50 values are close to those reported for vascular smooth muscle (VSM) cells, the SUR subtype may be similar to that in VSM cells, and could form the functional KATP channel in rat colonic smooth muscle cells.Key words: ATP-sensitive K+ channels, rat colonic smooth muscle cells, pinacidil, diazoxide, patch-clamp technique.