Taurine block of cloned ATP-sensitive K+ channels with different sulfonylurea receptor subunits expressed in Xenopus laevis oocytes

Jeong-Geun LimHyun-Young LeeJeung-Eun YunSang-Pyo KimJong-Wook ParkSeong-Il SuhByeong-Churl JangChi-Heum ChoJae-Hoon BaeSeong Soo KimJin HanMae Ja ParkDae-Kyu Song
Dept. of Neurology (신경과학); Dept. of Physiology (생리학); Dept. of Pathology (병리학); Dept. of Immunology (면역학); Dept. of Microbiology (미생물학); Dept. of Molecular Medicine (분자의학); Dept. of Obstetrics & Gynecology (산부인과학)
Issue Date
Biochemical Pharmacology, Vol.68(5) : 901-910, 2004
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. Keywords Taurine; KATP-channel; Sulfonylurea; Xenopus oocyte; Kir6.2; SUR
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Neurology (신경과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
Keimyung Author(s)
임정근; 김상표; 박종욱; 서성일; 장병철; 조치흠; 배재훈; 송대규
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