Inhibition of ATP-sensitive K+ channels by taurine through a benzamido-binding site on sulfonylurea receptor 1.
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.
Chronic Disease Research Center, Keimyung University School of Medicine, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, South Korea.
Eun-Jee
EJ
Park
Jae Hoon
JH
Bae
So-Yeon
SY
Kim
Jeong-Geun
JG
Lim
Won-Ki
WK
Baek
Taeg Kyu
TK
Kwon
Seong-Il
SI
Suh
Jong-Wook
JW
Park
In-Kyu
IK
Lee
Frances M
FM
Ashcroft
Dae-Kyu
DK
Song
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D013654:Taurine / Q000494:pharmacology*
D007328:Insulin; D008565:Membrane Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; D013453:Sulfonylurea Compounds; C117780:mitochondrial K(ATP) channel; D013654:Taurine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005905:Glyburide