β-adrenergic stimulation increases the intra-SR Ca termination threshold for spontaneous Ca waves in cardiac myocytes.

β-adrenergic stimulation of cardiac myocytes enhances intracellular calcium cycling, which frequently associates with pro-arrhythmic Ca waves. The threshold level of free calcium in the sarcoplasmic reticulum ([Ca]SR) where waves initiate is increased during β-adrenergic stimulation.1 Here, we measured [Ca]SR directly to monitor the [Ca]SR level at which spontaneous Ca waves terminated (termination threshold) during β-adrenergic stimulation. Compared with control conditions, application of the β-adrenergic receptor agonist isoproterenol (ISO; 1 μM) resulted in an increase in basal [Ca]SR and an increase in the [Ca]SR at which spontaneous Ca waves terminated. When [Ca]SR was experimentally matched, ISO stimulation resulted in a decrease in the depletion amplitude of the waves. Sensitization of ryanodine receptor SR Ca release channels to Ca with a low dose of caffeine in the presence of ISO was able to decrease the termination threshold compared with control conditions. Therefore, the Ca wave termination l...