Connexin 43 is involved in the sympathetic atrial fibrillation in canine and canine atrial myocytes

Objective: Atrial fibrillation (AF) is the most common rapid cardiac arrhythmia associated with high morbidity and mortality. Stimulation of the sympathetic nerve is involved in AF occurrence. The gap junction protein connexin 43 (Cx43) plays a key role in electrical conduction velocity in cardiac tissues, and under expression of Cx43 was linked with AF. The aim of this study was to investigate whether Cx43 was involved in sympathetic AF. Methods: Fifteen dogs were randomly divided into 3 groups (5 in each group). Sympathetic AF was induced in dogs and isolated canine atrial myocytes by isoproterenol (ISO) perfusion and rapid atrium pacing (RAP). The expression levels of nerve growth factor (NGF) and tyrosine hydroxylase (TH) in the atrial tissues were detected using immunohistochemical staining. The transcription and protein expression of Cx43 in the AF cell model was measured. Subsequently, Cx43 was blocked by short interfering (si) RNA in atrial myocytes and the gap junctional intercellular communication was detected using the scrape-loading and dye transfer assay. Results: Sympathetic AF was successfully induced by a combination of ISO perfusion and RAP. The expression levels of NGF and TH were increased in the RAP group, and further increased in the RAP + ISO group. Tissue samples from the AF dogs had a lower Cx43 level than those of the control group (p<0.05). The expressions of mRNA and protein of Cx43 in sympathetic AF cell model decreased by 26% and 28%, respectively, when compared with the control group, with p<0.05. Silencing Cx43 in cells by siRNA could also efficiently reduce Cx43 expression. The relative levels of Cx45 mRNA were decreased by 73% compared with unaffected cells. The scrape-loading and dye transfer assay showed that gap junctional intercellular communication was hampered in the sympathetic AF cell model and silencing Cx43 could impede channel conduction. Conclusion: The results suggested that low expression of Cx43 was involved in sympathetic AF by influencing intercellular channel conduction. Intervention of Cx43 expression might be an appealing therapy to sympathetic AF. Keywords: