Slow conduction and gap junction remodeling in murine ventricle after chronic alcohol ingestion

Male C57BL/6J mice were given 36% alcohol in the drinking water. Those given blank water were used as control. Twelve weeks later, the phenotypic characteristics of the heart, including gap junctions and electrical properties were examined. In the alcohol group the ventricles contained a smaller size of cardiomyocytes and a higher density of capillary networks, compared to the control. Western blots showed that, after drinking alcohol, the content of connexin43 (Cx43) protein in the left ventricle was increased by 18% (p < 0.05). Consistently, immunoconfocal microscopy demonstrated that Cx43 gap junctions were up-regulated in the alcohol group with a disorganized distribution, compared to the control. Optical mapping showed that the alcohol group had a reduced conduction velocity (40 ± 18 vs 60 ± 7 cm/sec, p < 0.05) and a higher incidence of ventricular tachyarrhythmia (62% vs 30%, p < 0.05).Long-term excessive alcohol intake resulted in extensive cardiac remodeling, including changes in expression and distribution of gap junctions, growth of capillary network, reduction of cardiomyocyte size, and decrease of myocardial conduction.Excessive alcohol ingestion is harmful to the heart [1-4]. Previous studies have shown that manifestations of alcoholic cardiac suppression include mechanical dysfunction and electrical instability [5-7]. Physiologically, effective pumping of the heart requires coordination of contraction between individual cardiomyocytes, which depends mainly on the proper propagation of action potentials. Disturbance in the spread of action potential along the myocardium also plays a key role in the formation of cardiac arrhythmia. At the subcellular level, transmission of action potential between adjacent cardiomyocytes goes through gap junctions [8,9].Gap junctions, composed of molecules belonging to the connexin multi-gene family, are clusters of cell membrane protein channels, which in the ventricular working cardiomyocytes are mainly made of connexi