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

Abstract

Abstract. Some class I antiarrhythmic drugs induce a sporadic hypoglycemia by producing insulin secretion via inhibition of ATP-sensitive K + (K ATP ) channels of pancreatic β-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 Ca 2+ 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 K ATP channel in a concentration-dependent manner without affecting its unitary amplitude in inside-out membrane patches of single MIN6 cells, and the IC 50 values were 0.24 and 4.9 μM, respectively. The L-type Ca 2+ 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 K ATP channels in insulin-secreting cells, possibly due to its Ca 2+ channel-blocking action.

Comparative Analysis of Genetic Variations in the Nav1.5 Sodium Channel Subunits that Underlie Brugada Syndrome Using Patient-Specific iPSC-CMs

“…It is worth mentioning that the prolongation was more profound in the control cells. The downward trend appeared when the concentration reached 10 µM, we infer that the L-type calcium channel was blocked by quinidine at such concentration according to previous descriptions (34). There was no prominent effect on APD30 or APD50.…”

The possible mechanisms by which maternal hypothyroidism impairs insulin secretion in adult male offspring in rats

“…Batches of 10 islets were incubated in 1 ml Krebs–Ringer solution containing the appropriate glucose concentration (2.8 or 16.7 mmol l −1 ) and various secretagogues or required agonists/antagonists that act at various steps of the insulin secretion pathway. The tested secretagogues or inhibitors were glibenclamide (50–150 μmol l −1 ; Lehtihet et al ), diazoxide (250 μmol l −1 ; Koster et al ), arginine (20 mmol l −1 ), nifedipine (0.1–10 μmol l −1 ; Nishida et al ) and NiCl 2 (100 μmol l −1 ; Bhattacharjee et al ). In the experiments in which the extracellular concentration of KCl was raised to 30 mmol l −1 , the concentration of NaCl was decreased to maintain the osmolarity.…”

Novel members of quinoline compound family enhance insulin secretion in RIN-5AH beta cells and in rat pancreatic islet microtissue

“…Additional reference compounds were also used in the assay. Quinidine, chloroquine, mefloquine (quinoline compounds) and the fluoroquinolone drugs gatifloxacin and levofloxacin were described to have an inhibitory effect on K ATP channels which may lead to membrane depolarization and subsequent increase of [Ca 2+ ] i in beta cells16171819. In RIN-5AH beta cells the insulin secretion was stimulated by quinidine and chloroquine at 50 μM but not by fluoroquinolones.…”