Modulation of cellular calcium stores in the perfused rat heart by isoproterenol and ryanodine.
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.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D004533:Egtazic Acid / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D000470:Alkaloids; D002132:Calcium Radioisotopes; D012433:Ryanodine; D011343:Procaine; D004533:Egtazic Acid; D007545:Isoproterenol; D002118:Calcium