Inhibition of ATP-Sensitive K+ Channels and L-Type Ca2+ Channels by Amiodarone Elicits Contradictory Effect on Insulin Secretion in MIN6 Cells
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概要
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Some class I antiarrhythmic drugs induce a sporadic hypoglycemia by producing insulin secretion via inhibition of ATP-sensitive K+ (KATP) channels of pancreatic β-cells. It remains undetermined whether amiodarone produces insulin secretion by inhibiting KATP channels. In this study, effects of amiodarone on KATP channels, L-type Ca2+ channel, membrane potential, and insulin secretion were examined and compared with those of quinidine in a β-cell line (MIN6). Amiodarone as well as quinidine inhibited the openings of the KATP channel in a concentration-dependent manner without affecting its unitary amplitude in inside-out membrane patches of single MIN6 cells, and the IC50 values were 0.24 and 4.9 μM, respectively. The L-type Ca2+ current was also inhibited by amiodarone as well as quinidine in a concentration-dependent manner. Although glibenclamide (0.1 μM) or quinidine (10 μM) significantly potentiated the insulin secretion from MIN6 cells, amiodarone (1 – 30 μM) failed to increase insulin secretion. Amiodarone (30 μM) and nifedipine (10 μM) significantly inhibited the increase in insulin secretion produced by 0.1 μM glibenclamide. Amiodarone (30 μM) produced a gradual decrease of the membrane potential, but did not produce repetitive electrical activity in MIN6 cells. Glibenclamide (1 μM) produced a slow depolarization, followed by spiking activity which was inhibited by 30 μM amiodarone. Thus, amiodarone is unlikely to produce hypoglycemia in spite of potent inhibitory action on KATP channels in insulin-secreting cells, possibly due to its Ca2+ channel–blocking action.
著者
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Nakaya Haruaki
Department Of Orthopaedic Surgery And Pharmacology School Of Medicine Chiba University
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Miki Takashi
Department Of 2nd. Surgery Kurume Univ. School Of Medicine
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SEINO Susumu
Division of Cellular and Molecular Medicine Kobe University Graduate School of Medicine
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Matsumoto Akio
Department Of Biochemistry Osaka University Medical School
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Nishida Atsushi
Department Of Chemical System Engineering The University Of Tokyo
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Takizawa Taichi
Department of Pharmacology, Chiba University Graduate School of Medicine, Japan
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Takizawa Taichi
Department Of Pharmacology Chiba University Graduate School Of Medicine
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Nishida Atsushi
Department Of Pharmacology Chiba University Graduate School Of Medicine
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