Inhibition of ATP-sensitive K+ channels by taurine through a benzamido-binding site on sulfonylurea receptor 1.
Park, Eun-Jee a,1; Bae, Jae Hoon b,1; Kim, So-Yeon b; Lim, Jeong-Geun a; Baek, Won-Ki a; Kwon, Taeg Kyu a; Suh, Seong-il a; Park, Jong-Wook a; Lee, In-Kyu a; Ashcroft, Frances M. c; Song, Dae-Kyu b,*
[Article] Biochemical Pharmacology. 67(6):1089-1096, March 15, 2004.

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ATP-sensitive potassium (KATP) 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 KATP channel activity in rat pancreatic [beta]-cells using the patch-clamp technique. The mechanism of taurine action was also examined using recombinant KATP channels. The islets and single [beta]-cells from male Sprague-Dawley rats were collected by collagenase digestion technique. Single KATP 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 KATP 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 KATP 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 Kir6.2[DELTA]C36 currents, a truncated form of Kir6.2, expressed in Xenopus oocytes without SUR. These results demonstrate that taurine inhibits the KATP channel activity in the [beta]-cells, interacting with a benzamido-binding site on SUR1, but not Kir6.2.

(C) 2004Elsevier, Inc.