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

• DOI: 10.1016/j.bcp.2003.11.003
• Publication Date: 2003-12-31T11:00:10Z
• Authors: Eun-Jee Park; Jae Hoon Bae; So-Yeon Kim; Jeong-Geun Lim; Won-Ki Baek; Taeg Kyu Kwon; Seong-il Suh; Jong-Wook Park; In-Kyu Lee; Frances M. Ashcroft; Dae-Kyu Song
• Keywords: Male; 0301 basic medicine; Binding Sites; Potassium Channels; 572; Taurine; Membrane Proteins; Rats; Adenosine Diphosphate; Rats, Sprague-Dawley; Islets of Langerhans; Protein Subunits; 03 medical and health sciences; Adenosine Triphosphate; Sulfonylurea Compounds; Glyburide; Animals; Insulin; Drug Interactions; Potassium Channels, Inwardly Rectifying

ATP-sensitive potassium (K(ATP)) channels in pancreatic beta-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 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 -60mV. Cytosolic free-Ca(2+) concentration ([Ca(2+)](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 [Ca(2+)](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.