A novel antagonist, No. 7943, of the Na+/Ca2+ exchange current in guinea‐pig cardiac ventricular cells

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Abstract
The effects of No. 7943 on the Na+/Ca2+ exchange current and on other membrane currents were investigated in single cardiac ventricular cells of guinea‐pig with the whole‐cell voltage‐clamp technique. No. 7943 at 0.1–10 μm suppressed the outward Na+/Ca2+ exchange current in a concentration‐dependent manner. The suppression was reversible and the IC50 value was approximately 0.32 μm. No. 7943 at 5–50 μm suppressed also the inward Na+/Ca2+ exchange current in a concentration‐dependent manner but with a higher IC50 value of approximately 17 μm. In a concentration‐response curve, No. 7943 raised the KmCa2+ value, but did not affect the Imax value, indicating that No. 7943 is a competitive antagonist with external Ca2+ for the outward Na+/Ca2+ exchange current. The voltage‐gated Na+ current, Ca2+ current and the inward rectifier K+ current were also inhibited by No. 7943 with IC50s of approximately 14, 8 and 7 μm, respectively. In contrast to No. 7943, 3′,4′‐dichlorobenzamil (DCB) at 3–30 μm suppressed the inward Na+/Ca2+ exchange current with IC50 of 17 μm, but did not affect the outward exchange current at these concentrations. We conclude that No. 7943 inhibits the outward Na+/Ca2+ exchange current more potently than any other currents as a competitive inhibitor with external Ca2+. This effect is in contrast to DCB which preferentially inhibits the inward rather than the outward Na+/Ca2+ exchange current.