Yasuhide Watanabe1,* and Junko Kimura2
1Department of Ecology and Clinical Therapeutics, School of Nursing and 2Department of Pharmacology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
*Corresponding author. FAX: +81-24-547-2361, E-mail: w-yasu@fmu.ac.jp
Abstract: We examined the effect of bepridil, a class IV antiarrhythmic drug, on Na+/Ca2+ exchange current (INCX) 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 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 INCX in a concentration-dependent manner. The IC50 value was 8.1 μM 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 μM bepridil inhibited INCX by 46 ± 7% (n = 8), while bepridil blocked it by 28 ± 8% (n = 6) in the presence of albumin. Bepridil inhibited INCX in a supra-therapeutic concentration range.
Keywords: Antiarrhythmic drug, Bepridil, Na+/Ca2+ exchange current, Whole-cell clamp, Cardiac myocyte
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