Monensin potentiation of potassium contracture in cat myocardium

A. L. Bassett, J. R. Wiggins, H. Gelband, B. C. Pressman

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)966-975
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume207
Issue number3
StatePublished - Dec 1 1978

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Monensin potentiation of potassium contracture in cat myocardium'. Together they form a unique fingerprint.

  • Cite this

    Bassett, A. L., Wiggins, J. R., Gelband, H., & Pressman, B. C. (1978). Monensin potentiation of potassium contracture in cat myocardium. Journal of Pharmacology and Experimental Therapeutics, 207(3), 966-975.