Effect of ryanodine on neonatal and adult rat heart: developmental increase in sarcoplasmic reticulum function.

Negative inotropic responses to nicardipine, MnCl2 and ryanodine of isolated papillary muscles were compared between 1-day-old neonatal and adult rats. All of the drugs produced dose-dependent negative inotropic responses at both ages. Nicardipine and MnCl2 were effective at lower concentrations in the neonate when compared to the adult, while ryanodine was more effective in the adult. Attenuation of the positive inotropic effect of isoproterenol by nicardipine was greater in the neonate, while that by ryanodine was greater in the adult. The relaxation phase of contraction was shortened by isoproterenol and prolonged by ryanodine in adult preparations, but there were no changes in the neonatal preparations. In the adult, increasing the stimulus frequency resulted in a decrease in contractile force (negative force-frequency relationship) at control conditions, while it produced rather slight increases in contractile force in the presence of ryanodine. In the neonate, increases in the stimulus frequency resulted in an increase in contractile force (positive force-frequency relationship) both in the presence and absence of ryanodine. It was concluded that contraction of the adult rat myocardium is highly dependent on Ca2+ release from the sarcoplasmic reticulum, while that of the neonatal myocardium is more dependent on trans-sarcolemmal Ca2+ influx. It was also speculated that the negative force-frequency relationship is produced by some factor(s) closely related to sarcoplasmic reticulum function.