MARKED DEPENDENCE OF THE CARDIAC EFFECTS OF GALLOPAMIL ON THE EXTRACELLULAR K+-CONCENTRATION

1. In guinea-pig Langendorff hearts, the negative inotropic effect of the calcium antagonist gallopamil is shifted by 15-fold to the left, when the extracellular K+-concentration is raised from 2.7 to 8.1 mM. 2. In papillary muscles, the ability of gallopamil to shorten the action potential (AP) markedly depends on K+: 100-fold lower gallopamil concentrations were required at 10.8 mM, compared to 2.7 mM. 3. In isolated myocytes, a change in the holding potential from -90 to -70 mV displaces the gallopamil dose-response curve to block Ca2+ currents leftward by only 6-fold. 4. Tetraethylammonium (TEA, 10 mM) mimics the mitigating effect of low K+ on the gallopamil-induced AP-shortening. Hence, the K+-dependence of gallopamil may be comprised of modulation of Ca2+-channel and K+-channel blocking effects.