Connexins and cardiac arrhythmias

Abstract

During cardiac remodeling, impulse conduction in the heart is altered by changes in excitability, electrical coupling, and tissue architecture. The impairment of normal impulse conduction is one of the factors that increases the propensity for arrhythmias. This chapter focuses on the relationship between electrical coupling between ventricular myocytes and arrhythmogenesis. Mouse models of decreased electrical coupling in the heart have shown that a clinically relevant 50% reduction in gap junctions in the heart has no effect on impulse conduction or arrhythmogenesis. To impair conduction and arrhythmias, coupling has to be reduced to very low levels. Apparently, there is a large conduction reserve, which can preserve normal impulse conduction even when electrical coupling is moderately reduced. However, cardiac remodeling is also associated with reduced excitability and increased levels of collagen deposition (fibrosis). It is therefore presumably the combination of, in itself ineffective, reduction of electrical coupling with other impairments like fibrosis or reduced excitability that causes the limits of conduction reserve to be exceeded, thereby resulting in abnormal impulse conduction and enhanced arrhythmogenesis.