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Depressing effects of calcium antagonists on oxygen consumption in isolated skeletal muscle during potassium
1Department of Health, Texas A & M University, College Station 77843.
Abstract:
The effects of two Ca2+-antagonizing drugs, dantrolene sodium (DAN) and TMB-8, on subcontracture, K+-induced increased oxygen consumption were studied in isolated frog sartorius muscles. Incubation in Ringer's solution +18 mM KCl caused a marked increase in averaged resting oxygen uptake (52.8 +/- 4.1 to 278.2 +/- 20.0 mm3.g-1.h-1). Incubation in Ringer's +18 mM KCl containing either 0.116 mM TMB-8 or 0.035 mM DAN resulted in a significant reduction in the averaged metabolic response (264.4 +/- 30.8 (control) vs. 142.3 +/- 19.0 (TMB-8) vs. 72.2 +/- 3.4 (DAN]. The results suggest that the enhanced metabolic rate observed upon elevating extracellular [K+] to just below contracture levels is due to increased intracellular Ca2+ release.
Insights
Two calcium-antagonizing drugs, dantrolene sodium (DAN) and TMB-8, significantly reduced potassium-induced oxygen consumption in frog muscles. This suggests that elevated extracellular potassium increases muscle metabolism via intracellular calcium release.
Area of Science:
- Muscle physiology
- Pharmacology
- Cellular metabolism
Background:
- Potassium (K+)-induced increases in muscle oxygen consumption are linked to cellular mechanisms.
- Calcium ions (Ca2+) play a crucial role in muscle contraction and metabolic regulation.
Purpose of the Study:
- To investigate the role of intracellular calcium release in K+-induced metabolic responses in isolated frog muscles.
- To evaluate the efficacy of Ca2+-antagonizing drugs, dantrolene sodium (DAN) and TMB-8, in modulating these responses.
Main Methods:
- Isolated frog sartorius muscles were used.
- Muscles were exposed to Ringer's solution with 18 mM KCl to induce metabolic changes.
- The effects of dantrolene sodium (DAN) and TMB-8 on oxygen consumption were measured.
Main Results:
- High extracellular K+ significantly increased resting oxygen uptake in frog muscles.
- Both TMB-8 and DAN markedly reduced this K+-induced increase in oxygen consumption.
- Dantrolene sodium showed a more pronounced inhibitory effect compared to TMB-8.
Conclusions:
- The enhanced metabolic rate induced by elevated extracellular K+ is likely mediated by increased intracellular Ca2+ release.
- Ca2+-antagonizing drugs effectively inhibit this metabolic response, supporting the role of calcium.
- These findings contribute to understanding the mechanisms of metabolic regulation in muscle tissue.