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Possible cyclic nucleotide regulation of calcium mediating myocardial contraction

A Schwartz, M L Endman, E G Ezrailson

    Science (New York, N.Y.)
    |March 11, 1977
    PubMed

    Insights

    Cyclic nucleotides, by inhibiting adenylate and guanylate cyclases, modulate calcium signaling in rabbit heart atria. This inhibition blocks catecholamine and acetylcholine effects, altering cardiac contractility and frequency responses.

    Area of Science:

    • Cardiovascular Physiology
    • Cellular Signaling
    • Pharmacology

    Background:

    • Adenylate and guanylate cyclases are key enzymes in cellular signaling pathways.
    • Cyclic nucleotides play crucial roles in regulating cardiac function.
    • Understanding the modulation of cardiac contractility by these pathways is vital.

    Purpose of the Study:

    • To investigate the role of cyclic nucleotides in modulating cardiac responses.
    • To determine the effects of inhibiting adenylate and guanylate cyclases on atrial contractility.
    • To elucidate the interaction between cyclic nucleotides and calcium in cardiac function.

    Main Methods:

    • Isolated rabbit left atrial strips were used for experimentation.
    • The effects of an adenylate and guanylate cyclase inhibitor were assessed.
    • Responses to catecholamines, acetylcholine, ouabain, and calcium were measured.

    Main Results:

    • Inhibition of cyclic nucleotide synthesis blocked catecholamine and acetylcholine effects.
    • The positive force-frequency relationship was converted to a negative one.
    • Ouabain induced contracture but not positive inotropy; increased calcium's cardiotonic effect persisted.

    Conclusions:

    • Cyclic nucleotides significantly modulate calcium-dependent cardiac responses.
    • Inhibition of these enzymes alters the response to various cardiotonic and cardiodepressive agents.
    • Data suggest a critical role for cyclic nucleotides in the calcium-associated modulation of cardiac stimuli.

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