title: Gap Junction-associated Na+ Influx Is Involved in the Mediation of Ca2+ Transients in Neonatal Rat Ventricular Myocytes.
abstract: Gap junction (GJ) coupling is involved in the regulation of spontaneous Ca(2+) transients in neonatal rat ventricular myocytes (NRVMs); however, the underlying mechanism(s) remains incompletely clear. In this study, we investigated Na influx mediated by Cx43-associated GJ modulating the spontaneous NRVM excitation. Intracellular Na(+) and Ca(2+) concentrations ([Na(+)](i) and [Ca(2+)](i)) were assessed using CoroNa Green and Fluo-4 fluorescent probes, respectively, by confocal microscopy. GJ function was evaluated by measuring fluorescence recovery after photobleaching. The results showed that [Na(+)](i) and spontaneous Ca(2+) oscillating were significantly decreased by the treatment of NRVMs with GJ uncouplers or adenovirus-mediated Cx43 gene knockdown using short hairpin RNA, while both of the intracellular cation levels were increased by adenovirus-mediated Cx43 overexpression. Neither Na(+) channel blocker (tetrodotoxin) nor the GJ uncoupler (Gap27) or Cx43-short hairpin RNA adenovirus could completely suppress the Ca(2+) transients, but their combination usage could. In addition, Ca(2+) transients disappeared in NRVMs incubated in Na(+)-free, but not in Ca(2+) -free medium, in which the remained transients could be further abolished by Gap27. Collectively, our findings suggest that Cx43-associated GJ function is involved in the regulation of Na(+) influx into cardiomyocytes, which contributes, at least in part, to triggering spontaneous excitation and regulation of cardiomyocyte automaticity.
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, China (Li is now with the National Institute for Radiological Protection, China CDC, Beijing, China).
authors.forename: Xinxin
authors.initials: X
authors.lastname: Yan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zeng
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Dali
authors.initials: D
authors.lastname: Luo
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology*; D006352:Heart Ventricles; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D012964:Sodium / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology
chemical_list: D018031:Connexin 43; C580592:Gja1 protein, rat; D015222:Sodium Channels; D012964:Sodium