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Lookup NU author(s): Dr Fiona LeBeauORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
BackgroundAlpha-synuclein is associated with neurodegeneration in Parkinson's disease (PD). Recent studies have increasingly recognized incidences of cardiac complaints in PD patients. In particular, the occurrence 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 membranes. However, the effect of alpha-synuclein on the heart and sympathetic neuronal tissues remains unknown.ObjectiveThis study investigated the electrophysiological effects of alpha-synuclein aggregates in myocardium and cardiac sympathetic nervous system, potentially reflecting cardiac electrophysiological alteration in PD.MethodsWe measured the in situ sodium and potassium currents from murine ventricular myocardium and stellate ganglia using the loose patch clamp technique. The tissues were exposed to bioactive alpha-synuclein aggregates, and currents were measured under three different conditions: baseline, alpha-synuclein treatment, and wash out.ResultsThe experiments showed that alpha-synuclein aggregates altered the maximum cardiac 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.ConclusionsOur results demonstrate that extracellular alpha-synuclein aggregates can inhibit ventricular but not stellate ganglion ionic currents, suggesting a differential sensitivity between the myocardium and the stellate ganglia, and indicating a cardiac-specific toxicity of alpha-synuclein on cardiac electrophysiology.Alpha-synuclein is the pathological hallmark of Parkinson's disease (PD). There is an increased recognition of incidences of heart-related complaints in PD patients. In particular, arrhythmias have been associated with PD. This may indicate potential pathological changes in the heart. Alpha-synuclein has been known to be toxic to mammalian cells. However, its effect has not been tested in the heart and heart-connecting nerve tissues. Therefore, we investigated the effect of alpha-synuclein aggregates on the heart and the heart-connecting nervous tissues. The heart and stellate ganglia conveying nerves to the heart were exposed to bioactive alpha-synuclein aggregates, and the ionic current in these tissues were measured. The results showed that alpha-synuclein aggregates reduced the size of the inward sodium current in the heart. However, the alpha-synuclein aggregates did not affect the ionic currents in the stellate ganglia. Our results revealed that alpha-synuclein aggregates can alter cardiac ionic currents, which imply that a cardiac-specific toxicity of alpha-synuclein aggregates on cardiac electrophysiology in PD.
Author(s): Lee B, Ahmad S, Edling CE, Matthews HR, Huang CL-H, LeBeau FE, Jeevaratnam K
Publication type: Article
Publication status: Published
Journal: Journal of Parkinson's disease
Year: 2025
Volume: 15
Issue: 7
Pages: 1194-1207
Print publication date: 01/11/2025
Online publication date: 28/08/2025
Acceptance date: 16/07/2025
Date deposited: 27/11/2025
ISSN (print): 1877-7171
ISSN (electronic): 1877-718X
Publisher: Sage
URL: https://doi.org/10.1177/1877718X251365239
DOI: 10.1177/1877718X251365239
Data Access Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request
PubMed id: 40874712
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