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. INCX was recorded by ramp pulses from the holding potential of -60 mV in the presence of 140 mM Na+ and I 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 INCX in a concentration-dependent manner. The IC50 value was 8.1 muM with a Hill coeff-icient 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 muM bepridil inhibited T-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.