Ion channels play a vital role in cardiac electrophysiology by modulating the inotropic and chronotropic action and the cardiac electrophysiology in turn is modulated by the autonomic nervous system (ANS). In recent years studies have shown a correlation between cardiac disease and Parkinson’s disease (PD) which features the degeneration of ANS. However, the mechanism causing the evident cardiac denervation in PD remains unclear. A30P missense mutation of alpha-synuclein is a risk factor of familial PD, and alpha-synucleinopathy is the hallmark of PD. We aimed to investigate the link between alpha-synucleinopathy and cardiac ion channel remodelling with the aid of the A30P transgenic PD mice model.

For our studies, eight groups of wildtypes and A30P transgenic mice, young and old, male and female were investigated (n = 4 each group, total 32 samples). We performed RNA-sequencing of the heart and stellate ganglia. Immunohistochemistry was conducted to investigate the mutant protein expression. Our data revealed that the A30P transgenic mice present with mutant alpha-synuclein in the heart and stellate ganglia and with up-regulated pro/anti-inflammatory markers on the mRNA level. Additionally, the mRNA expression of cardiac ion channels was significantly changed.

Our results indicate that mutation of alpha-synuclein can result in alterations in cardiac and sympathetic ganglionic tissue including cardiac ion channel remodelling and an inflammatory reaction following alpha-synucleinopathy development. To investigate further we aim to study the phenotype of the electrophysiological modifications. In conclusion, here we demonstrate a transcriptional link between the ANS and cardiac electrophysiology which can help identify and explain the increased risk of cardiac disease in PD patients.