Taurine block of cloned ATP-sensitive K+ channels with different sulfonylurea receptor subunits expressed in Xenopus laevis oocytes.
Taurine has been found to inhibit ATP-sensitive K+ (KATP) channels in rat pancreatic beta-cells [Park et al., Biochem Pharmacol 2004;67:1089-1096] which could be due to its interaction with a benzamido-binding site on SUR1. In present study, we further evaluated the mechanism of taurine action on the KATP-channel inhibition, using cloned KATP-channels with different types of SUR subunit expressed in Xenopus laevis oocytes. The oocytes were coinjected with Kir6.2 mRNA, and mRNA encoding SUR1, SUR2A or SUR2B. Macroscopic currents were recorded from giant excised inside-out patches. The binding of glibenclamide to SUR1 was assessed by using a glibenclamide-fluorescent probe. Intracellular taurine inhibited all three types of KATP-channels to a similar extent. They were fit to the Hill equation, showing IC50 of 11.0 mM for Kir6.2/SUR1, 10.9 mM for Kir6.2/SUR2A, and 9.0 mM for Kir6.2/SUR2B currents. Taurine at the concentration of 10 mM enhanced the high-affinity bindings of glibenclamide and repaglinide on all types of SUR, whereas the low-affinity binding on Kir6.2 was not affected. The intensity of glibenclamide fluorescence was higher in the plasma membrane of taurine-pretreated oocytes. The high-affinity binding of tolbutamide or gliclazide on SUR was not modified by taurine. These results suggest that the taurine inhibition of KATP-channels is mediated by an interaction with the site on SUR where the benzamido group is bound. Therefore, intracellular concentrations of taurine in different tissues may be more important in determining taurine modulation of the KATP-channel rather than distinct types of SUR subunit.
Department of Neurology, Keimyung University School of Medicine, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, South Korea.
Jeong-Geun
JG
Lim
Hyun-Young
HY
Lee
Jeung-Eun
JE
Yun
Sang-Pyo
SP
Kim
Jong-Wook
JW
Park
Seong-Il
SI
Suh
Byeong-Churl
BC
Jang
Chi-Heum
CH
Cho
Jae-Hoon
JH
Bae
Seong Soo
SS
Kim
Jin
J
Han
Mae Ja
MJ
Park
Dae-Kyu
DK
Song
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D002219:Carbamates / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D005907:Gliclazide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009865:Oocytes; D010880:Piperidines / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits / Q000037:antagonists & inhibitors* / Q000235:genetics; D051381:Rats; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000235:genetics; D064233:Sulfonylurea Receptors; D013654:Taurine / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology; D014982:Xenopus laevis
D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; C577509:Abcc8 protein, rat; C577511:Abcc9 protein, mouse; D002219:Carbamates; D007004:Hypoglycemic Agents; D008565:Membrane Proteins; D010880:Piperidines; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; C117780:mitochondrial K(ATP) channel; D013654:Taurine; C072379:repaglinide; D014044:Tolbutamide; D005907:Gliclazide; D005905:Glyburide