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

Abstract

ATP-sensitive potassium (K ATP) channels in pancreatic β-cells comprise sulfonylurea receptor (SUR) 1 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 β-cells using the patch-clamp technique. The mechanism of taurine action was also examined using recombinant K ATP channels. The islets and single β-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-Ca 2+ concentration ([Ca 2+] c) and insulin secretory capacity were measured by the dual-excitation fluorimetry and radioimmunoassay, respectively. The native β-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 [Ca 2+] c and increased insulin secretion in the β-cells when pretreated with taurine. Taurine did not inhibit Kir6.2ΔC36 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 β-cells, interacting with a benzamido-binding site on SUR1, but not Kir6.2.