Expression of connexin in atrium of patients with atrial fibrillation and its signal transduction pathway

Abstract

To explore the expression of connexin (Cx) and its signal transduction pathway in the atrium of patients with atrial fibrillation (AF). Atrial tissue samples of 63 patients undergoing cardiac surgery, including patients with chronic AF or paroxysmal AF (PAF), and those with sinus rhythm, were collected during operation. The mRNA expressions of calcineurin B and mitogen-activated protein kinase-1 (MKP-1) were detected by semi-quantitative RT-PCR. The protein expressions of extracellular-signal regulated kinase 1 (ERK1), phospho-ERK1 (P-ERK1), Cx40 and Cx43 were analyzed by Western blotting. HE staining and immunohistochemistry were used to examine the distribution of Cx40 and Cx 43. Increased amounts of Cx40 protein (left atrium: 2.2 +/- 0.8, 2.2 +/- 0.6; right appendages: 2.1 +/- 0.5, 2.0 +/- 0.8) were found in the left atrium and right appendages of patients with Chronic persistent AF (CAF) or paroxysmal AF (PAF) (P < 0.05). The expression of Cx43 was only increased in the left atrium of patients with CAF and PAF (3.1 +/- 0.6, 2.8 +/- 0.7 vs 1.0 +/- 0.2, both P < 0.05). The amounts of Calcineurin B mRNA, MKP-1 mRNA and P-ERK1 of patients with CAF or PAF were significantly increased compared with patients in sinus rhythm (P < 0.05). Immunohistochemistry revealed that Cx40 and Cx43 of CAF patients and PAF patients acculmated in the intracellular site, and at the lateral member of atrial cells, both connexins redistributed. The increased expression and disorderly distribution of Cx 40 and Cx 43 protein in the atrium of AF patients may be related with the abnormal activation and disequilibria of regulation of ERK1, MKP-1 and calcineurin.