Inhibitory effect of amiodarone on Na(+)/Ca(2+) exchange current in guinea-pig cardiac myocytes.

The effect of amiodarone on Na(+)/Ca(2+) exchange current (I(NCX)) was examined in single guinea-pig ventricular myocytes using the whole-cell voltage clamp technique. I(NCX) was recorded by ramp pulses from the holding potential of -60 mV in the presence of 140 mM Na(+) and 2 mM Ca(2+) in the external solution, and 20 mM Na(+) and 398 nM free Ca(2+) (19 mM Ca(2+) and 30 mM BAPTA) in the internal solution. External application of amiodarone suppressed I(NCX) in a concentration-dependent manner. The IC(50) value was 3.3 microM with a Hill coefficient of 1. Intracellular application of trypsin via the micropipette attenuated the blocking effect of amiodarone, suggesting that amiodarone affects the cytoplasmic side of the molecule. This inhibitory effect of amiodarone on the Na(+)/Ca(2+) exchanger may contribute to the cardioprotective action of the drug.