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. 1988 Nov;82(5):1592–1605. doi: 10.1172/JCI113771

Role of intracellular sodium in the regulation of intracellular calcium and contractility. Effects of DPI 201-106 on excitation-contraction coupling in human ventricular myocardium.

J K Gwathmey 1, M T Slawsky 1, G M Briggs 1, J P Morgan 1
PMCID: PMC442728  PMID: 2460503

Abstract

Experiments were performed to investigate the mechanism of action of DPI 201-106 on human heart muscle. In both control and myopathic muscles, DPI produced concentration-dependent increases in action potential duration, resting muscle tension, peak isometric tension, and duration of isometric tension. These changes were associated with increases in resting intracellular calcium and peak calcium transients as measured by aequorin. At higher concentrations of DPI, a second delayed Ca2+ transient (L') appeared. L' was inhibited by tetrodotoxin and ryanodine, suggesting that DPI acts at both the sarcolemma and the sarcoplasmic reticulum. DPI toxicity was manifested by after-glimmers and after-contractions reflecting a Ca2+-overload state: DPI effects were mimicked by veratridine, a Na+ channel agonist, and reversed by tetrodotoxin, yohimbine, and cadmium, Na+ channel antagonists. These results suggest that DPI acts primarily as a Na+ channel agonist. DPI may produce an increase in intracellular Ca2+ by increasing intracellular Na+ and altering Na+-Ca2+ exchange across the sarcolemma. DPI may also increase intracellular Ca2+ by directly altering sarcoplasmic reticulum Ca2+ handling.

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Selected References

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