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

Coexpression of sulfonylurea receptor (SUR) and inward-rectifying K+ channe l (Kir6.1 or 6.2) subunit yields ATP-sensitive K+ (K-ATP) channels. Three s ubtypes of SUR have been cloned: pancreatic (SUR1), cardiac (SUR2A), and va scular smooth muscle (SUR2B). The distinct responses to K+ channel openers (KCOs) produced in different tissues may depend on the SUR isoform of K-ATP channel. Therefore, we investigated the effects of pinacidil and diazoxide , two KCOs, on K-ATP 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 hol ding potential of -70 mV. The reversal potential of the stimulated current was about -75 mV, which is close to the equilibrium potential for K+ (E-K) Both pinacidil and diazoxide dose-dependently stimulated K+ currents (evoke d by ramp pulses), with EC50 values of 1.3 and 34.2 mu M, respectively The stimulated current was completely reversed by glybenclamide (3 mu M). Since the EC50 values are close to those reported for vascular smooth muscle (VS M) cells, the SUR subtype may be similar to that in VSM cells, and could fo rm the functional K-ATP channel in rat colonic smooth muscle cells.