Blocking effect of bepridil on Na+/Ca2+ exchange current in guinea pig cardiac ventricular myocytes

We examined the effect of bepridil, a class IV antiarrhythmic drug, on Na+/Ca2+ exchange current (I(NCX)) in single guinea pig cardiac ventricular cells 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 1 mM Ca2+ in the external solution and 20 mM Na+ and 119 nM free Ca2+ (7 mM Ca2+ and 20 mM BAPTA) in the internal solution. Bepridil suppressed I(NCX) in a concentration-dependent manner. The IC50 value was 8.1 microM with a Hill coefficient of 0.8. Intracellular treatment with trypsin via the pipette solution attenuated the blocking effect of bepridil, suggesting that the inhibitory site is on the cytosolic side of the Na+/Ca2+ exchanger. In the absence of albumin in the external solution, 10 microM bepridil inhibited I(NCX) by 46+/-7% (n = 8), while bepridil blocked it by 28+/-8% (n = 6) in the presence of albumin. Bepridil inhibited I(NCX) in a supra-therapeutic concentration range.