Background: Alpha-synuclein, the major constituent of Lewy bodies (LB), is associated with neurodegeneration in Parkinson’s disease (PD). Recent studies have reported an increasing recognition of cardiac complaints in PD patients and the cardiac pathologies associated with alpha-synuclein (Javanshiri et al. 2023; Lee et al. 2023). Particularly, the development of arrhythmias in PD patients may indicate potential electrophysiological alterations in the heart. Alpha-synuclein aggregates have been known to have disruptive effects on cell electrophysiology (Schmidt et al. 2012; Ferreira et al. 2017). However, their effect on the neurocardiac system has remained unknown.
Objectives: We investigated whether the exogenous application of alpha-synuclein aggregates affects the ventricular myocardium and stellate ganglia, potentially disrupting the electrophysiological integrity of the neurocardiac system.
Methods: We measured the in situ sodium and potassium currents from murine ventricular myocardium and stellate ganglia using the loose patch clamp technique (Lee et al. 2025). Male mice (C57BL/6) tissues were collected (n = 6 per group), followed by decapitation, conforming to the institutional guidelines (AWERB review reference: NASPA-1819-25 Amend 1) and the Animal (Scientific Procedures) Act. The tissues were exposed to bioactive extracellular alpha-synuclein aggregates, and currents were measured under three different conditions: baseline, alpha-synuclein treatment, and wash out (n = 18 patches per group, from six independent experiments).
Results: The result showed that alpha-synuclein aggregates altered the maximum sodium current (INa(Max)) (ANOVA, p < 0.008) and affected its gating properties for channel activation (ANOVA F2,54 = 6.408, p = 0.003) and inactivation (F2, 67 = 6.32, p = 0.003). The alpha-synuclein aggregates also reduced the maximum outward potassium current (IK(Max)) during channel activation (F2, 77 = 6.02, p = 0.002). However, the alpha-synuclein aggregates did not affect the ionic currents in the stellate ganglia.
Conclusion: Our results demonstrated that alpha-synuclein aggregates can inhibit ventricular ionic currents but do not affect the stellate ganglia, suggesting differential sensitivity between the myocardium and the stellate ganglia and indicating cardiac-specific toxicity of alpha-synuclein on cardiac electrophysiology in PD.