ROLE OF SARCOPLASMIC-RETICULUM IN MYOCARDIAL-CONTRACTION OF NEONATAL AND ADULT MICE

Changes in action potential parameters by and inotropic responses to n icardipine, verapamil, ryanodine and cyclopiazonic acid were examined in isolated ventricular myocardial preparations from neonatal and adul t mice. The action potential of both neonatal and adult mice had a uni que configuration with little evidence of a plateau at depolarized mem brane potential; the action potential duration was significantly large r in neonatal preparations. Nicardipine had no effect on action potent ial parameters in the adult while it significantly shortened the actio n potential duration at 50% repolarization in the neonate. Ryanodine s ignificantly shortened the action potential duration at 80% repolariza tion at both ages: the shortening was significantly larger in the adul t when compared with the neonate. The contraction of ventricular prepa rations from adult mice were relatively resistant to nicardipine and v erapamil. Nicardipine or verapamil, even at 10(-5) M, only decreased t he contractile force to 70% of control values; the decrease was much l ess than that reported in other experimental species such as chick, gu inea pig or rabbit. In the neonate, 10(-5) M nicardipine or verapamil decreased the contractile force to 30% of control values. Ryanodine ha d a potent negative inotropic effect both in the neonate and adult; th e effect was significantly larger in the adult. Cyclopiazonic acid pro duced a decrease in contractile force and prolongation of the time req uired for relaxation; both effects were significantly larger in the ad ult. These results suggest that the contraction of the adult mouse myo cardium is highly dependent on SR function and less dependent on trans sarcolemmal Ca2+ influx when compared with the myocardium of the neona tal mouse and that of other species. (C) 1998 Elsevier Science Inc. Al l rights reserved.