BACKGROUND AND PURPOSEWe investigated the influence of metoprolol on gap junction proteins connexin43 (Cx43) and connexin40 (Cx40) in atrial tissue from patients with/without atrial fibrillation (AF). EXPERIMENTAL APPROACHLeft atrial tissue samples from 160 patients with AF or sinus rhythm (SR) with or without metoprolol (mean daily dose: 65.2 Ϯ 9.1 mg·day -1 ) were analysed for Cx43 and Cx40 by Western blot and immunohistology. Transverse and longitudinal conduction velocities were determined by 64 multi-electrode mapping. KEY RESULTSBoth Cx43 and Cx40 expression were significantly increased in patients with AF versus SR. Cx43-expression in AF was significantly higher in patients receiving metoprolol, while Cx40 expression was unaffected by metoprolol treatment. In AF, the ratio of lateral/polar expression of Cx43 and Cx40 was enhanced due to increased expression at the sides of the cells (lateral) and a loss at the cell poles. This AF-induced increase in lateral/polar expression of Cx43, but not of Cx40, was significantly antagonized by metoprolol treatment. Functionally, in AF patients, transverse conduction velocity in atrial samples was significantly enhanced and this change was also significantly antagonized by metoprolol. CONCLUSIONS AND IMPLICATIONSAF induced enhanced lateral expression of Cx43 and Cx40 together with enhanced transverse conduction velocity in left atrial tissue. Alterations in localization of Cx43 and conduction changes were both antagonized by metoprolol, showing that pharmacological modulation of gap junction remodelling seems, in principle, possible. This finding may open new approaches to the development of anti-arrythmic drugs. AbbreviationsAF, atrial fibrillation; CHD, coronary heart disease; Cx40, connexin40; Cx43, connexin43; EF, ejection fraction; FITC, Fluorescein isothiocyanate; GAPDH, glyceraldehyde-3-phosphate-dehydrogenase; LM, length of the plasma membrane; MVD, mitral valve disease; PLM, length of the immunofluorescence-positive membrane; SR, sinus rhythm; TBS, Tris-buffered saline; V(L), longitudinal conduction velocity; V(T), transverse conduction velocity BJP British Journal of Pharmacology

Enhanced BMI is associated with increased remodeling effects of AF on irregular Cx43 distribution.

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