2020 - Homocysteine-induced electrical remodeling via the mediation of IP 3 R1/Nav1.5 signaling pathway
Port-a-Patch publication in American Journal of Translational Research (2020)
Han L., Wu A., Li Q., Xia Z., Wu Y., Hong K., Xia Z., Li J.
American Journal of Translational Research (2020) PMID: 32774738
Inositol-1,4,5-triphosphate-receptor 1 (IP3R1), a Ca2+ channel in the sarcoplasmic reticulum membrane, is an effective regulator of Ca2+ release involved in the pathology of most cardiovascular diseases. Our study aim to investigate the underlying mechanism by which IP3R1 signaling mediates the process of homocysteine (Hcy)-induced Ca2+ accumulation via interaction with sodium current (Nav1.5) in atrium. We utilized whole-cell patch-clamp analysis and flow cytometry to detect the abnormal electrical activity in mouse atrial myocytes (MACs) obtained from C57B6 mice fed with high-Hcy diet. The results represented not only an increase in protein levels of Nav1.5 and IP3R1, but also an enhanced intracellular levels of Ca2+, and prolonged action potential duration (APD). However, the inhibition of IP3R1 or Nav1.5 gene could both attenuate Ca2+ accumulation in MACs triggered by Hcy, as well as abnormal electrical activity. In addition, Hcy increased the interaction between IP3R1 and Nav1.5. These data suggest that Hcy induced Ca2+ accumulation is mediated by the IP3R1/Nav1.5 signaling pathway, accompanied with the influx of Na+ and Ca2+, which act as triggers for electrical remodeling.