What question did this study set out to answer?

To investigate the cellular mechanisms by which DPI 201-106 influences excitation-contraction coupling and calcium handling in control and myopathic human ventricular myocardium.

November 1, 1988Journal of Clinical InvestigationOpen Access

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.

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Population

Human ventricular myocardium (control and myopathic muscles)

Design

Preclinical

Authors

JGJudith K. GwathmeyHeart Failure & Transplant MSMara SlawskyBaystate Medical Center GBGeorge M. BriggsUniversity of Arkansas at Little Rock

Discussion

Member takes

Implication

Raises caution for calcium overload toxicity with Na+ agonists; leaves open translation to human inotropic therapy.

Key Points

To investigate the cellular mechanisms by which DPI 201-106 influences excitation-contraction coupling and calcium handling in control and myopathic human ventricular myocardium.
Evaluated the pharmacological effects of DPI 201-106 on isolated control and myopathic human heart muscle preparations.
Recorded action potential duration, resting and peak isometric muscle tension, and intracellular calcium transients using aequorin luminescence.
Assessed responses to sodium channel modulators (veratridine, tetrodotoxin, yohimbine, cadmium) and the sarcoplasmic reticulum inhibitor ryanodine.
DPI 201-106 produced concentration-dependent increases in action potential duration, resting tension, peak isometric tension, and peak calcium transients in both control and myopathic myocardium.
Higher concentrations induced a secondary delayed calcium transient (L') that was blocked by tetrodotoxin and ryanodine, alongside toxic after-contractions and after-glimmers indicating calcium overload.
Pharmacological effects were replicated by the sodium channel agonist veratridine and reversed by sodium channel antagonists, indicating that DPI 201-106 increases calcium primarily through enhanced sodium influx and altered sodium-calcium exchange.

Structured PICO

Population

Human ventricular myocardium (control and myopathic muscles)

Intervention

DPI 201-106

Outcome

Action potential duration, resting muscle tension, peak isometric tension, duration of isometric tension, and intracellular calcium transientssurrogate

DPI 201-106 acts primarily as a Na+ channel agonist to increase intracellular calcium and contractility in human ventricular myocardium, but can cause calcium overload toxicity.

Cite This Study

Gwathmey et al. (1988) studied this question.

synapsesocial.com/papers/6a718c788031ec7bb1dd04a3 https://doi.org/10.1172/jci113771

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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.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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Also Consider