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 language | English |
|---|---|
| Pages (from-to) | 966-975 |
| Number of pages | 10 |
| Journal | Journal of Pharmacology and Experimental Therapeutics |
| Volume | 207 |
| Issue number | 3 |
| State | Published - Dec 1 1978 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
Cite this
Monensin potentiation of potassium contracture in cat myocardium. / Bassett, A. L.; Wiggins, J. R.; Gelband, H.; Pressman, B. C.
In: Journal of Pharmacology and Experimental Therapeutics, Vol. 207, No. 3, 01.12.1978, p. 966-975.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Monensin potentiation of potassium contracture in cat myocardium
AU - Bassett, A. L.
AU - Wiggins, J. R.
AU - Gelband, H.
AU - Pressman, B. C.
PY - 1978/12/1
Y1 - 1978/12/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 32383
AN - SCOPUS:0018231556
VL - 207
SP - 966
EP - 975
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 3
ER -