Journal of Pharmacological Sciences (Jan 2011)

Inhibition of ATP-Sensitive K+ Channels and L-Type Ca2+ Channels by Amiodarone Elicits Contradictory Effect on Insulin Secretion in MIN6 Cells

  • Atsushi Nishida,
  • Taichi Takizawa,
  • Akio Matsumoto,
  • Takashi Miki,
  • Susumu Seino,
  • Haruaki Nakaya

DOI
https://doi.org/10.1254/jphs.10294fp
Journal volume & issue
Vol. 116, no. 1
pp. 73 – 80

Abstract

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Abstract.: 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 chan-nels in insulin-secreting cells, possibly due to its Ca2+ channel–blocking action. Keywords:: ATP-sensitive K+ channel, amiodarone, quinidine, insulin, β-cell