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

Some class I antiarrhythmic drugs induce a sporadic hypoglycemia by producing insulin secretion via inhibition of ATP-sensitive K+ (K-ATP) channels of pancreatic beta-cells. It remains undetermined whether amiodarone produces insulin secretion by inhibiting K-ATP channels. In this study, effects of amiodarone on K-ATP channels, L-type Ca2+ channel, membrane potential, and insulin secretion were examined and compared with those of quinidine in a beta-cell line (MIN6). Amiodarone as well as quinidine inhibited the openings of the K-ATP 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 mu M, respectively. The L-type Ca2+ current was also inhibited by amiodarone as well as quinidine in a concentration-dependent manner. Although glibenclamide (0.1 mu M) or quinidine (10 mu M) significantly potentiated the insulin secretion from MIN6 cells, amiodarone (1 - 30 mu M) failed to increase insulin secretion. Amiodarone (30 mu M) and nifedipine (10 mu M) significantly inhibited the increase in insulin secretion produced by 0.1 mu M glibenclamide. Amiodarone (30 mu M) produced a gradual decrease of the membrane potential, but did not produce repetitive electrical activity in MIN6 cells. Glibenclamide (1 mu M) produced a slow depolarization, followed by spiking activity which was inhibited by 30 mu M amiodarone. Thus, amiodarone is unlikely to produce hypoglycemia in spite of potent inhibitory action on K-ATP channels in insulin-secreting cells, possibly due to its Ca2+ channel-blocking action.