Ceramide modulates electrophysiological characteristics and oxidative stress of pulmonary vein cardiomyocytes

Shih Yu Huang, Yen Yu Lu, Yung Kuo Lin, Yao Chang Chen, Yi Ann Chen, Cheng Chih Chung, Wei Shiang Lin, Shih Ann Chen, Yi Jen Chen

研究成果: 雜誌貢獻文章同行評審

摘要

Background: Ceramide is involved in regulating metabolism and energy expenditure, and its abnormal myocardial accumulation may contribute to heart injury or lipotoxic cardiomyopathy. Whether ceramide can modulate the electrophysiology of pulmonary veins (PVs) remains unknown. Materials and methods: We used conventional microelectrodes to measure the electrical activity of isolated rabbit PV tissue preparations before and after treatment with various concentrations of ceramide with or without H2O2 (2 mM), MitoQ, wortmannin or 740 YP. A whole-cell patch clamp and fluorescence imaging were used to record the ionic currents, calcium (Ca2+) transients, and intracellular reactive oxygen species (ROS) and sodium (Na+) in isolated single PV cardiomyocytes before and after ceramide (1 μM) treatment. Results: Ceramide (0.1, 0.3, 1 and 3 μM) reduced the beating rate of PV tissues. Furthermore, ceramide (1 μM) suppressed the 2 mM H2O2-induced faster PV beating rate, triggered activities and burst firings, which were further reduced by MitoQ. In the presence of wortmannin, ceramide did not change the PV beating rate. The H2O2-induced faster PV beating rate could be counteracted by MitoQ or wortmannin with no additive effect from the ceramide. Ceramide inhibited pPI3K. Ceramide reduced Ca2+ transients, sarcoplasmic reticulum Ca2+ contents, L-type Ca2+ currents, Na+ currents, late Na+ currents, Na+-hydrogen exchange currents, and intracellular ROS and Na+ in PV cardiomyocytes, but did not change Na+-Ca2+ exchange currents. Conclusion: C2 ceramide may exert the distinctive electrophysiological effect of modulating PV activities, which may be affected by PI3K pathway–mediated oxidative stress, and might play a role in the pathogenesis of PV arrhythmogenesis.
原文英語
文章編號e13690
期刊European Journal of Clinical Investigation
52
發行號4
DOIs
出版狀態已發佈 - 4月 2022

ASJC Scopus subject areas

  • 生物化學
  • 臨床生物化學

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