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 Ca(2+)-channel and K(+)-channel blocking effects.
Herzig
S
S
Department of Pharmacology, University of Kiel, Fed. Rep. Germany.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D005711:Gallopamil / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects; D011188:Potassium / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015220:Calcium Channels; D013757:Tetraethylammonium Compounds; D005711:Gallopamil; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium