Inhibition of ATP-sensitive K+ channels by taurine through a benzamido-binding site on sulfonylurea receptor 1

ATP-sensitive potassium (K-ATP) channels in pancreatic beta-cells comprise sulfonylurea receptor (SUR) I and inwardly-rectifying potassium channel (Kir) 6.2 subunits. We have evaluated the effect of intracellular taurine on K-ATP channel activity in rat pancreatic beta-cells using the patch-clamp technique. The mechanism of taurine action was also examined using recombinant K-ATP channels. The islets and single beta-cells from male Sprague-Dawley rats were collected by collagenase digestion technique. Single K-ATP channel currents were recorded by the inside-out mode at a membrane potential of -60 mV. Cytosolic free-Ca2+ concentration ([Ca2+](c)) and insulin secretory capacity were measured by the dual-excitation fluorimetry and radioimmunoassay, respectively. The native beta-cell K-ATP channel was directly inhibited by taurine in a dose-dependent manner. Taurine did not influence ATP-mediated inhibition or MgADP-induced activation of the channel activity. The sensitivity of the K-ATP channel to glybenclamide, but not gliclazide, was enhanced by taurine. Glybenclamide elicited a greater increase in [Ca2+](c) and increased insulin secretion in the beta-cells when pretreated with taurine. Taurine did not inhibit Kir6.2DeltaC36 currents, a truncated form of Kir6.2, expressed in Xenopus oocytes without SUR. These results demonstrate that taurine inhibits the K-ATP channel activity in the beta-cells, interacting with a benzamido-binding site on SUR1, but not Kir6.2. (C) 2003 Elsevier Inc. All rights reserved.