Comparative study of the effects of salinomycin and monensin on electrophysiologic and contractile properties of canine myocardium.
The effects of the monocarboxylic ionophore, salinomycin (K+-selective), on isometric twitches, 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 X 10(-6) M) which did not produce changes in resting force, salinomycin increased peak active force (Po, + 170 +/- 36%, mean % change from control +/- S.D., P less than 0.01), and maximal rates of force development (dP/dt max, + 123 +/- 33%, P less than 0.01) and relaxation (-dP/dt max, + 180 +/- 40%, P less than 0.01) of the isometric twitch. A similar response pattern was found for 5 X 10(-6) M monensin (Po, + 90 +/- 24%, P less than 0.01; dP/dt max, + 137 +/- 19%, P less than 0.01; -dP/dt max, + 145 +/- 20%, P less than 0.01). In contrast to their effects on isometric twitches, salinomycin reduced peak K+ contracture force (Pc, -35 +/- 14%, P less than 0.01) whereas monensin increased it (Pc, + 30 +/- 12%, P less than 0.02). Ventricular muscle action potential duration was shortened similarly by the ionophores. beta-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.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004285:Dogs; D004594:Electrophysiology; D005663:Furans / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology*; D007537:Isometric Contraction; D008985:Monensin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology; D000095662:Polyether Polyketides
D002395:Catecholamines; D005663:Furans; D007476:Ionophores; D008985:Monensin; D011188:Potassium; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides