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

Eun-Jee ParkJae Hoon BaeSo-Yeon KimJeong-Geun LimWon-Ki BaekTaeg Kyu KwonSeong-il SuhJong-Wook ParkIn-Kyu LeeFrances M. AshcroftDae-Kyu Song
Dept. of Physiology (생리학); Dept. of Neurology (신경과학); Dept. of Microbiology (미생물학); Dept. of Immunology (면역학); Dept. of Internal Medicine (내과학)
Issue Date
Biochemical Pharmacology, Vol.67(6) : 1089-1096, 2004
ATP-sensitive potassium (KATP) 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 KATP channel activity in rat pancreatic β-cells using the patch-clamp technique. The mechanism of taurine action was also examined using recombinant KATP channels. The islets and single β-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 β-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 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 KATP channel activity in the β-cells, interacting with a benzamido-binding site on SUR1, but not Kir6.2. Keywords Taurine; ATP-sensitive potassium channel; Sulfonylurea; Ca2+ concentration; Insulin; Pancreatic β-cell
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1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Neurology (신경과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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임정근; 백원기; 권택규; 서성일; 박종욱; 이인규; 배재훈; 송대규
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