Where is the origin of the activator calcium in cardiac ventricular contraction?

Under normal experimental conditions, the force of rested-state contractions (i.e., contractions after a rest period of 15 min or longer) of mammalian ventricular myocardium is insignificant. In Mg2+-free solution, in low sodium solution or in the presence of a cardioactive steroid, a strong "early" rested-state contraction develops without delay after stimulation, indicating the accumulation during rest of intracellularly stored activator calcium. By contrast, catecholamines cause a "late" rested-state contraction with a characteristic latent period of about 100 ms between stimulation and onset of contraction. Inhibition of the slow inward current by nifedipine has no influence on the contraction velocity of the "early" rested-state contraction, indicating that Ca2+ of the slow inward current is not involved in the calcium release mechanism of prefilled stores during excitation-contraction coupling. Nifedipine suppresses the "late" rested-state contraction in the presence of noradrenaline. In view of the constancy of the latent period, it is proposed that the activator calcium for the "late" rested-state contraction enters the cell with the slow inward current, is sequestered at first by uptake sites of the sarcoplasmic reticulum and subsequently released from its release sites as long as the cell is depolarized. The model of the different origin of activator calcium is discussed in its implication for high-frequency contractions.