Inhibition of ATP-Sensitive K^+ Channels and L-Type Ca^<2+> Channels by Amiodarone Elicits Contradictory Effect on Insulin Secretion in MIN6 Cells

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Abstract

Some class I antiarrhythmic drugs induce a sporadic hypoglycemia by producing insulin secretion via inhibition of ATP-sensitive K<SUP>+</SUP> (K<SUB>ATP</SUB>) channels of pancreatic <I>β</I>-cells. It remains undetermined whether amiodarone produces insulin secretion by inhibiting K<SUB>ATP</SUB> channels. In this study, effects of amiodarone on K<SUB>ATP</SUB> channels, L-type Ca<SUP>2+</SUP> channel, membrane potential, and insulin secretion were examined and compared with those of quinidine in a <I>β</I>-cell line (MIN6). Amiodarone as well as quinidine inhibited the openings of the K<SUB>ATP</SUB> channel in a concentration-dependent manner without affecting its unitary amplitude in inside-out membrane patches of single MIN6 cells, and the IC<SUB>50</SUB> values were 0.24 and 4.9 <I>μ</I>M, respectively. The L-type Ca<SUP>2+</SUP> current was also inhibited by amiodarone as well as quinidine in a concentration-dependent manner. Although glibenclamide (0.1 <I>μ</I>M) or quinidine (10 <I>μ</I>M) significantly potentiated the insulin secretion from MIN6 cells, amiodarone (1 – 30 <I>μ</I>M) failed to increase insulin secretion. Amiodarone (30 <I>μ</I>M) and nifedipine (10 <I>μ</I>M) significantly inhibited the increase in insulin secretion produced by 0.1 <I>μ</I>M glibenclamide. Amiodarone (30 <I>μ</I>M) produced a gradual decrease of the membrane potential, but did not produce repetitive electrical activity in MIN6 cells. Glibenclamide (1 <I>μ</I>M) produced a slow depolarization, followed by spiking activity which was inhibited by 30 <I>μ</I>M amiodarone. Thus, amiodarone is unlikely to produce hypoglycemia in spite of potent inhibitory action on K<SUB>ATP</SUB> channels in insulin-secreting cells, possibly due to its Ca<SUP>2+</SUP> channel–blocking action.

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 116(1), 73-80, 2011-05-20

    The Japanese Pharmacological Society

References:  39

Cited by:  1

Codes

  • NII Article ID (NAID)
    10029894018
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13478613
  • NDL Article ID
    11083066
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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