The role of the Cx43/Cx45 gap junction voltage gating on wave propagation and arrhythmogenic activity in cardiac tissue

Abstract

Gap junctions (GJs) formed of connexin (Cx) protein are the main conduits of electrical signals in the heart. Studies indicate that the transitional zone of the atrioventricular (AV) node contains heterotypic Cx43/Cx45 GJ channels which are highly sensitive to transjunctional voltage (Vj). To investigate the putative role of Vj gating of Cx43/Cx45 channels, we performed electrophysiological recordings in cell cultures and developed a novel mathematical/computational model which, for the first time, combines GJ channel Vj gating with a model of membrane excitability to simulate a spread of electrical pulses in 2D. Our simulation and electrophysiological data show that Vj transients during the spread of cardiac excitation can significantly affect the junctional conductance (gj) of Cx43/Cx45 GJs in a direction- and frequency-dependent manner. Subsequent simulation data indicate that such pulse-rate-dependent regulation of gj may have a physiological role in delaying impulse propagation through the AV node. We have also considered the putative role of the Cx43/Cx45 channel gating during pathological impulse propagation. Our simulation data show that Vj gating-induced changes in gj can cause the drift and subsequent termination of spiral waves of excitation. As a result, the development of fibrillation-like processes was significantly reduced in 2D clusters, which contained Vj-sensitive Cx43/Cx45 channels.