Monensin potentiation of potassium contracture in cat myocardium

The cardiac inotropic action of a Na⁺-selective carboxylic ionophore, monensin, was evaluated in isolated cat right ventricular muscle during beta adrenergic blockade (nadolol, 10^-4 M). Exposure to low concentrations of monensin (10^-8-10^-7 M) for 30 min either had no effect or decreased force of isometric contraction (P₀) at 0.33 Hz, whereas higher concentrations (10^-6-10^-5 M) increased both P₀ and dP/dt. Monensin, 10^-5 M, had no effect on resting force when the bathing solution contained 2.7 mM Ca⁺⁺ but increased resting force when the bathing solution contained 5.4 mM Ca⁺⁺. Monensin (≥10^-6 M) had little effect on force developed during contracture evoked by 133 mM KCl when the ionophore was added during an ongoing contracture. However, treatment with monensin (≥10^-6 M) in beta blocked muscles before K⁺ depolarization increased contracture force in a concentration-dependent manner. A similar increase in contracture force by monensin occurred in unstimulated muscles. These effects of monensin on K⁺ contracture force were abolished by removal of Na⁺ from the bathing solution and were enhanced by increasing Ca⁺⁺ to 5.4 mM in the presence of Na⁺. Monensin reduced Na⁺-lack contracture. Positive inotropic effects of monensin on K⁺ contracture and contraction also occurred during combined beta and alpha adrenergic blockade (phenoxybenzamine, 10^-5 M). Our data suggest that prior contractions are not necessary for monensin potentiation of P₀ and contracture, provided extracellular Na⁺ is present and sufficient time is available for monensin to transport this cation. Because monensin transports Ca⁺⁺ poorly compared to Na⁺, we infer that the primary effect of monensin is to alter Na⁺, which in turn modulates Ca⁺ and alters the contractile state of the myocardium.