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  • Title: Pharmacological evidence for two types of myocardial sarcoplasmic reticulum Ca2+ release.
    Author: Lynch C.
    Journal: Am J Physiol; 1991 Mar; 260(3 Pt 2):H785-95. PubMed ID: 1705758.
    Abstract:
    Contractions of guinea pig papillary muscles were studied at 37 degrees C under a variety of conditions and stimulation rates that markedly alter the pattern of tension development. When rested-state contractions (RSCs) were enhanced by treatments that increase intracellular adenosine 3',5'-cyclic monophosphate (0.1-1 microM isoproterenol, 1-10 microM forskolin), a markedly enhanced late peak tension developed after a 100-ms delay. Such late peak tension was selectively depressed by local anesthetics (200-400 microM procaine, 4-10 microM tetracaine, or 0.5-1 mM ethyl aminobenzoate). In contrast, 0.1-1 microM ryanodine had little effect on late peak tension, whereas 5 mM caffeine reduced the delay before tension development. Inotropic interventions such as increased external Ca2+ concentration or the Ca2+ channel agonist BAY K 8644 did not elicit such distinct late peaking RSCs. Rapid initial tension development observed under a variety of situations (short cycle lengths, stimulation rates of 0.25 Hz plus isoproterenol, decreased external Na+ concentration) was markedly depressed by 0.01-1 microM ryanodine and by caffeine, whereas local anesthetics had little effect. These results suggest two pharmacologically distinct types of sarcoplasmic reticulum Ca2+ release: 1) Ca2+ that accumulates during prior depolarizations is released immediately upon depolarization and decreased by ryanodine and caffeine; 2) extracellular Ca2+ that enters the myocyte is accumulated and released after an initial delay and is selectively depressed by low concentrations of local anesthetics.
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