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  • Title: Modulation of cellular calcium stores in the perfused rat heart by isoproterenol and ryanodine.
    Author: Hunter DR, Haworth RA, Berkoff HA.
    Journal: Circ Res; 1983 Nov; 53(5):703-12. PubMed ID: 6414734.
    Abstract:
    The inhibitory action of procaine on cellular calcium release was utilized to define a new cellular calcium pool which, under physiological conditions, is present only during catecholamine stimulation. Rat hearts labeled with 45Ca++ were perfused with medium containing procaine and EGTA at 23 degrees C to remove extracellular calcium, and then cellular calcium was released by removal of procaine and restoration of calcium. By this method we have identified a cellular calcium pool (pool C) whose release is inhibited by procaine, but which does not require extracellular calcium for its release. Release of pool C can also be triggered by caffeine. [We have previously identified a cellular calcium pool (pool A) whose release is triggered by caffeine, inhibited by procaine, and which does require extracellular calcium for its release.] When hearts were labeled for 3 minutes with perfusate containing 1 mM 45Ca++, 48 +/- 6 nmol Ca++/g wet weight was found in pool A, but only 3 +/- 1 nmol Ca++/g in pool C. However, if isoproterenol was present during labeling, the hearts contained 72 +/- 5 nmol Ca++/g in pool A and 42 +/- 6 nmol Ca++/g in pool C. When calcium concentration in the labeling perfusate was varied, with and without isoproterenol, it was found that pool C does not begin to fill until pool A is almost full. The same effect was seen when excess cellular calcium uptake was induced by removing sodium from the perfusate. Ryanodine (0.2 microM) induced contractile failure (t1/2 = 3.4 +/- 0.4 min) and depleted pool A in control hearts by 85%. Ryanodine also similarly depleted pools A and C in isoproterenol-treated hearts. When contractility was monitored at the same time as the hearts were labeled, a linear relationship between dP/dt and the sum of pools A and C was observed over a wide range of conditions. Pools A and C both selected strongly for calcium over barium. These observations suggest that both pools A and C are located in the sarcoplasmic reticulum and are intimately involved in the regulation of contractility.
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