Key result
Inhibition of the Na+/Ca2+ exchanger by SEA0400 significantly decreased the Ca2+ transient frequency in guinea pig pulmonary vein cardiomyocytes from 1.82 Hz to 0.62 Hz, but had no effect in sinus node cardiomyocytes.
Why the study?
The role of the Na+/Ca2+ exchanger in automaticity of pulmonary vein cardiomyocytes, a potential ectopic pacemaker that may cause atrial fibrillation, compared with sinus node cardiomyocytes, needed evaluation.
Absolute Event Rate: 0.62% vs 1.82%
p-value: p=0.0006
The forward mode of the Na+/Ca2+ exchanger contributes to the spontaneous ectopic activity in pulmonary vein cardiomyocytes but not in the sinus node, highlighting a potential mechanism for atrial fibrillation triggers.
NCX inhibition selectively suppresses pulmonary vein ectopy in guinea pigs; hypothesis-generating for AF triggers, needs higher-order confirmation.
Fluorescence imaging analysis was performed in cardiomyocytes from the sinus node, the orthotopic pacemaker, and the pulmonary vein, a potential ectopic pacemaker that may cause atrial fibrillation, focusing on the role of the Na+/Ca2+ exchanger (NCX). Isolated cardiomyocytes from the guinea pig pulmonary vein and sinus node showing automaticity were loaded with fluorescence probes for analysis. Inhibition of NCX by SEA0400 decreased the Ca2+ transient frequency in the pulmonary vein cardiomyocytes but not in the sinus node. The basal intracellular Ca2+ concentration, as well as the number of Ca2+ sparks in the subsarcolemmal region, was higher in the pulmonary vein cardiomyocytes than in the sinus node. By contrast, the intracellular Na+ concentration was not different between the pulmonary vein and sinus node cardiomyocytes. The equilibrium potential for NCX (ENCX) was estimated to be less negative in the pulmonary vein cardiomyocytes than in the sinus node. In conclusion, the forward mode NCX is involved in spontaneous activity in the pulmonary vein cardiomyocytes but not in the sinus node; this is probably because the Ca2+ supply and the driving force for the forward mode NCX are both larger in the pulmonary vein cardiomyocytes than in the sinus node.
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Odaka et al. (2025) studied Automaticity of cardiomyocytes. SEA0400 vs. Baseline (before treatment) was evaluated on Ca2+ transient frequency in pulmonary vein cardiomyocytes (Hz) (p=0.0006). Inhibition of the Na+/Ca2+ exchanger by SEA0400 significantly decreased the Ca2+ transient frequency in guinea pig pulmonary vein cardiomyocytes from 1.82 Hz to 0.62 Hz, but had no effect in sinus node cardiomyocytes.
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