Formation of Heterotypic Gap Junction Channels

Gap junctions formed between transfected cells expressing connexin (Cx) 40 and Cx43 (Cx43-RIN, Cx40-HeLa, and Cx43-HeLa) revealed a relationship, gj5f(Vj), at steady state, that is typified by a nonsymmetrical behavior similar to that previously reported for other heterotypic channels (gap junction conductance [gj]; transjunctional voltage [Vj]). The unitary conductance of the channels was sensitive to the polarity of Vj. A main state conductance of 61 pS was found when the Cx43 cell was stepped positively or the Cx40 cell negatively (Vj570 mV); the reverse polarities yielded a conductance of 100 pS. These heterotypic channels were permeable to carboxyfluorescein. In addition, two other heterotypic forms are illustrated to demonstrate that endogenous Cx45 expression cannot explain the results. The demonstration of heterotypic Cx40 –Cx43 channels may have implications for the propagation of the electrical impulse in heart. For example, they may contribute to the slowing of the impulse propagation through the junctions between Purkinje fibers and ventricular muscle. The full text of this article is available at http://www.circresaha.org. (Circ Res. 2000;86:e42-e49.)