EFFECTS OF RYANODINE ON CONTRACTILE-FORCE OF POTASSIUM-DEPOLARIZED HEARTS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 15  (3) , 511-523
Abstract
The relationship between cellular Ca movements and contractility was indirectly assessed in Langendorff-preparations of guinea pig hearts perfused with either Krebs-Henseleit solution or a high-K (22 mM) solution containing 2.4 .times. 10-8 M isoproterenol. The addition of either D600 [.alpha.-isopropyl-.alpha.-[N-methyl-N-homoveratryl-.alpha.-aminopropyl]-3,4,5-trimethoxyphenylacetonitrile] (2.4-24.0 .times. 10-8 M) or ryanodine (0.24-24.0 .times. 10-6 M) to hearts perfused with Krebs-Henseleit solution produced a concentration-dependent reduction in contractile force. In K-depolarized, isoproterenol-restored hearts, the negative inotropic action of D600 exhibited concentration- and time-dependent changes similar to those observed in Krebs-Henseleit solution. In contrast, addition of 0.24-75.0 .times. 10-6 M ryanodine to K-depolarized, isoproterenol-restored hearts produced a time-dependent reduction in tension followed by a concentration-dependent rebound in contractile force. These results were interpreted as a consequence of the respective actions of D600 and ryanodine on Ca2+ influx and on intracellular Ca stores.