Inhibition of ATP-sensitive K+ channels by taurine through
a benzamido-binding site on sulfonylurea receptor 1
- Affiliated Author(s)
- 임정근; 백원기; 권택규; 서성일; 박종욱; 이인규; 배재훈; 송대규
- Alternative Author(s)
- Lim, Jeong Geun; Baek, Won Ki; Kwon, Taeg Kyu; Suh, Seong Il; Park, Jong Wook; Lee, In Kyu; Bae, Jae Hoon; Song, Dae Kyu
- Journal Title
- Biochemical Pharmacology
- ISSN
- 0006-2952
- Issued Date
- 2004
- Abstract
- 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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