title: [Remodeling of cardiac gap junctions and arrhythmias].
abstract: In the heart, gap junctions mediate electrical and chemical coupling between adjacent cardiomyocytes, forming the cell-to-cell pathways for orderly spread of the wave of electrical excitation responsible for a functional syncytium. Three principal connexins are expressed in cardiomyocytes, connexin 43 (CX43), CX40, and CX45. CX43 predominates in ventricular muscle cells. Most of the gap junctions, assembled from CX43, are located at the intercalated discs, often with larger junctional plaques at the disc periphery. The gap junctions are rarely distributed to the sides of the cardiomyocyte. The ischemia-reperfusion, cardiac hypertrophy, heart failure, hypercholesterolemia, and diabetes mellitus induce gap junction remodeling. The gap junction remodeling induced by above-mentioned diseases shows similar characteristics, including down-regulation of CX43, reduction in gap junction plaque size, increased heterogeneity and lateralization of gap junction distribution, and dephosphorylation of CX43. The elevated angiotensin II concentration in local myocardium may play an important role in the gap junction remodeling. The down-regulation of CX43 and lateralization of gap junction distribution alter anisotropic spread of the impulse of ventricular myocardium. The dephosphorylation of CX43 not only reduces electrical conductance, but also decreases permeability of chemicals between cardiomyocytes. The lateralization of gap junctions may increase the number of hemichannels formed by CX43. The opening of hemichannels induces ATP efflux and Na(+) influx, which forms a delayed after-depolarization. The gap junction remodeling in pathological condition produces arrhythmia substrate in the ventricles. In this review, the current knowledge on the relationship between the remodeling of cardiac gap junctions and arrhythmias were summarized.
authors.affiliation: Department of Aerospace Physiology, the Fourth Military Medical University, Xi'an 710032, China. yuzhib@fmmu.edu.cn
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Yu
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Sheng
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002450:Cell Communication; D018031:Connexin 43 / Q000378:metabolism / Q000502:physiology*; D017630:Connexins / Q000378:metabolism / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D000097003:Gap Junction alpha-5 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D000097003:Gap Junction alpha-5 Protein; C082920:connexin 45