Résumé
Introduction Sinoatrial cells generate cardiac automaticity through functional interactions between membrane ionic currents and intracellular Ca²⁺ dynamics. Mitochondrial Ca²⁺ plays a role in ATP synthesis regulation and intracellular Ca²⁺ levels. Interestingly, both could modify AMPc levels and possibly regulate cardiac automatism. We then hypothesized that mitochondrial Ca²⁺ homeostasis interact with β-adrenergic pathways and regulates cardiac automatism. Objective To determine whether pharmacological inhibition of the mitochondrial Ca²⁺ uniporter (MCU), which is responsible for Ca²⁺ influx in mitochondria, affects the sinoatrial node function and β-adrenergic responses. Method Basal level and amplitude of Ca²⁺ transients were recorded using a ratiometric fluorescent probe (Fura-2/AM) in mice isolated sinoatrial cells. Optical voltage mapping was also used to study the spontaneous frequency of action potentials generated by intact sinoatrial tissue isolated from C57Bl6 mice. Results In basal conditions, inhibition of mitochondrial Ca²⁺ influx with Ru360 in isolated sinoatrial cells did not affect automaticity. On the other hand, Ru360 prevents intracellular Ca²⁺ increase after stimulation of L-type Ca²⁺ channels. Similarly, MCU inhibition applied to intact sinoatrial tissues did not show significant effects under basal conditions, but induced a significant reduction of the spontaneous frequency (PA/min) under β-adrenergic stimulation. Conclusion We here demonstrated that mitochondrial Ca²⁺ regulates intracellular Ca²⁺ dynamics, and that mitochondrial Ca²⁺ is needed to support cAMP production, by stimulating ATP synthesis during a β-adrenergic stimulation. We propose that this mechanism is required to maintain a high spontaneous frequency, especially under physiological stress conditions.