Effects of ryanodine on the contractile force of potassium-depolarized hearts

The relationship between cellular calcium movements and contractility was indirectly assessed in Langendorff-preparations of guinea pig hearts perfused with either Krebs-Henseleit solution or a high-potassium (22 mM) solution containing 2.4 X 10(-8) M isoproterenol. The addition of either D600 (2.4-24.0 X 10(-8) M) or ryanodine (0.24-24.0 X 10(-6) M) to hearts perfused with Krebs-Hanseleit solution produced a concentration-dependent reduction in contractile force. In potassium-depolarized, isoproterenol-restored hearts, the negative inotropic action of D600 exhibited concentration-and time-dependent changes similar to those observed in Krebs-Hanseleit solution. In contrast, addition of 0.24-75.0 X 10(6) M ryanodine to potassium-depolarized, isoproterenol-restored hearts produce a time-dependent reduction in tension followed by a concentration-dependent rebound in contractile force. These results have been interpreted to be a consequence of the respective actions of D600 and ryanodine on Ca2+ influx and on intracellular calcium stores.