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Aims: Atrial fibrillation AF has been associated with intracellular calcium disturbances in human atrial myocytes, but little is known about the potential influence of sex and we here aimed to address this issue. Methods and results: Alterations in calcium regulatory mechanisms were assessed in human atrial myocytes from patients without AF or with long-standing persistent or permanent AF. Patch-clamp measurements revealed that L-type calcium current ICa density was significantly smaller in males with than without AF In contrast, transient inward currents ITi were more frequent in females with than without AF 1.

Moreover, confocal calcium imaging showed that females with AF had more calcium spark sites than those without AF 9. This was linked to higher ryanodine receptor phosphorylation at s in women with AF, and inhibition of adenosine A2A or beta-adrenergic receptors that modulate s phosphorylation was able to reduce the higher incidence of ITI in women with AF.

Conclusion: Perturbations of the calcium homoeostasis in AF is sex-dependent, concurring with increased spontaneous SR calcium release-induced electrical activity in women but not in men, and with diminished ICa density in men only. Keywords: Afterdepolarizations; Calcium sparks; Ryanodine receptor phosphorylation; Sarcoplasmic reticulum calcium release; Transient inward current.

Abstract Aims: Atrial fibrillation AF has been associated with intracellular calcium disturbances in human atrial myocytes, but little is known about the potential influence of sex and we here aimed to address this issue.