| Abstrakt: |
The effects of the monocarboxylic ionophore, salinomycin (K+-selective), on isometric twitcches, high K+-induced contracture and transmembrane action potentials were compared with those of the monocarboxylic ionophore, monensin (Na+-selective), in isolated canine right ventricular muscle. In a concentration (5 × 10−6) which did not produce changes in resting force, salinomycin increased peak active force ( P0, + 170 ± 36%, mean % change from control ±S.D., P< 0.01). and relaxation and maximal rates of force development (dP/dtmax, + 123 ± 33%, P < 0.01) and relaxation (−dP/dtmax, + 180 ± 40%, P < 0.01) of the isometric twitch. A similar response pattern was found for 5 × 10−6M monensin (P0, + 90 ± 24%, P < 0.01; dP/dtmax, + 137 ± 19%, P < 0.01; −dP/dtmax, + 145 ± 20%, P < 0.01). In contrast to their effects on isometric twitches, salinomycin reduced peak K+contracture force (Pc, −35 ± 14%, P < 0.01) whereas monensin increased it (Pc, +30 ± 12%, P < 0.02). Ventricular muscle action potential duration was shortened similarly by the ionophores. β-Adrenergic receptor blockade with nadolol diminished salinomycin's effects on the isometric twitch and K+contracture, but not its effect to shorten the action potential. Monensin's actions were unaffected by nadolol. These results suggest that salinomycin's effects arise from both a direct modulation of K+movement and the release of endogenous catecholamine. In contrast, monensin may act to alter intracellular Na+which in turn leads to Na+Ca2+exchange and Ca2+-mediated modulation of K+movement. |
