Key result
Isoproterenol increases basal [Ca]SR and the spontaneous Ca wave termination threshold versus control.
Why the study?
β-adrenergic stimulation increases the threshold level of free calcium in the sarcoplasmic reticulum at which spontaneous Ca waves initiate, but the termination threshold during such stimulation was not measured.
β-adrenergic stimulation increases the Ca wave termination level, which may alter Ca depletion from the SR and reduce arrhythmogenic potential.
May refine β-adrenergic arrhythmia models at cellular level; leaves open clinical translation or therapeutic targeting.
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 level may represent an important mode of altering Ca depletion from the SR and reducing the arrhythmogenic potential during β-adrenergic stimulation.
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Maxwell et al. (2013) studied this question. Isoproterenol (ISO) vs. Control conditions was evaluated on [Ca]SR level at which spontaneous Ca waves terminated (termination threshold). Application of the β-adrenergic receptor agonist isoproterenol (1 μM) increased basal [Ca]SR and the [Ca]SR at which spontaneous Ca waves terminated compared with control conditions.
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