Electrolyte disturbances differentially regulate sinoatrial node and pulmonary vein electrical activity: A contribution to hypokalemia- or hyponatremia-induced atrial fibrillation

Background: Hypokalemia and hyponatremia increase the occurrence of atrial fibrillation. Sinoatrial nodes (SANs) and pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation. Objective: The purpose of this study was to evaluate whether electrolyte disturbances with low concentrations of potassium ([K⁺]) or sodium ([Na⁺]) modulate SAN and PV electrical activity and arrhythmogenesis, and to investigate potential underlying mechanisms. Methods: Conventional microelectrodes were used to record electrical activity in rabbit SAN and PV tissue preparations before and after perfusion with different low [K⁺] or [Na⁺], interacting with the Na⁺-Ca²⁺ exchanger inhibitor KB-R7943 (10 μΜ). Results: Low [K⁺] (3.5, 3, 2.5, and 2 mM) decreased beating rates in PV cardiomyocytes with genesis of delayed afterdepolarizations (DADs), burst firing, and increased diastolic tension. Low [K⁺] (3.5, 3, 2.5, and 2 mM) also decreased SAN beating rates, with genesis of DADs. Low [Na⁺] increased PV diastolic tension, DADs, and burst firing, which was attenuated in the co-superfusion with low [K⁺] (2 mM). In contrast, low [Na⁺] had little effect on SAN electrical activities. KB-R7943 (10 μΜ) reduced the occurrences of low [K⁺] (2 mM)- or low [Na⁺] (110 mM)-induced DAD and burst firing in both PVs and SANs. Conclusion: Low [K⁺] and low [Na⁺] differentially modulate SAN and PV electrical properties. Low [K⁺]- or low [Na⁺]-induced slowing of SAN beating rate and genesis of PV burst firing may contribute to the high occurrence of atrial fibrillation during hypokalemia or hyponatremia.