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)
Authors:
Han L., Wu A., Li Q., Xia Z., Wu Y., Hong K., Xia Z., Li J.
Journal:
American Journal of Translational Research (2020) PMID: 32774738
Introduction:
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.
