Ryanodine in mammalian heart ventricular muscle: indication for the induction of calcium leakage from the sarcoplasmic reticulum.

Ryanodine at nanomolar concentrations suppressed the earlier of two contraction components which can be produced in guinea-pig papillary muscles, in the presence of noradrenaline (3 microM) at a low contraction frequency (0.2 Hz). However, test contractions elicited shortly after a steady state contraction showed an unimpaired early contraction component. This component declined with increases in the interval preceding the test contraction at a rate depending on the ryanodine concentration (the apparent first-order rate constant 0.07 s-1 of the spontaneous decline was doubled by about 0.2 nM and was increased to 1.3 s-1 by 10 nM ryanodine). The effect of ryanodine resembled that of a potassium-induced depolarization with the exception that it was not antagonized by an increase in the extracellular magnesium concentration. It is concluded that ryanodine enhances the leakage of stored calcium in mammalian heart muscle, probably by a direct influence on the calcium release channels of the junctional sarcoplasmic reticulum of the heart muscle cell.