Junctional communication between isolated pairs of canine atrial cells is mediated by homogeneous and heterogeneous gap junction channels

Introduction: The expression of multiple connexins (Cxs) in the canine right atria raises the possibility that heterogeneous gap junction channels might be formed. Methods and Results: We compared the unitary conductance (gamma(j)) of gap junction channels between isolated canine atrial cell pairs with those of homogeneous cardiac gap junction channels expressed in other systems. After partial uncoupling with halothane (2 mmol/L), the gamma(j) calculations for atrial isolated cardiocytes ranged from 30 to 220 pS and their distribution in event histograms was spread over the entire range, with a small peak at similar to 100 pS. This distribution deviates from the discrete peaks calculated from gamma(j) of homogeneous channels. All-points histograms of junctional current traces revealed distinct open-state levels. Some of these are related to the main open state of connexin43 (Cx43) (similar to 100 pS), observed between canine ventricular cells, or connexin40 (Cx40) (similar to 215 pS) observed between transfected N2A cells under similar recording conditions. Intermediate values for gamma(j) were not observed in recordings from ventricular cells, which express mostly Cx43, nor in those from N2A cells expressing Cx40, but were observed consistently between atrial cells. Because they were measured as first openings from the nonconductance state, these intermediate values most likely represent main conductance states of heterogeneous channels rather than subconductance states of homogeneous channels. Conclusion: This suggests that regulation of cell-to-cell coupling in the heart depends not only on posttranslational modulation of preexisting Cxs, but also on the intracellular assembly mechanisms, and the way individual Cxs interact with others within a connexon and/or with other connexons from adjacent cells.