Ryanodine and cyclopiazonic acid were used to alter the ability of the sarcoplasmic reticulum (SR) to store calcium. Interventions of this kind significantly reduced the rate of spontaneous beating of guinea-pig sino-atrial node preparations. In addition, both of these drugs decreased the rate of rise and modified other characteristics of the action potentials recorded from this region. It is proposed that calcium released from the SR plays an important, previously unrecognized, role in pacemaking in the sino-atrial node, possibly through regulation of sarcolemmal ionic currents.

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