EVIDENCE FOR HETEROMERIC GAP JUNCTION CHANNELS FORMED FROM RAT CONNEXIN43 AND HUMAN CONNEXIN37

Homomeric gap junction channels are composed solely of one connexin ty pe, whereas heterotypic forms contain two homomeric hemichannels but t he six identical connexins of each are different from each other. A he teromeric gap junction channel is one that contains different connexin s within either or both hemichannels. The existence of heteromeric for ms has been suggested, and many cell types are known to coexpress conn exins. To determine if coexpressed connexins would form heteromers, we cotransfected rat connexin43 (rCx43) and human connexin37 (hCx37) int o a cell line normally devoid of any connexin expression and used dual whole cell patch clamp to compare the observed gap junction channel a ctivity with that seen in cells transfected only with rCx43 or hCx37. We also cocultured cells transfected with hCx37 or rCx43, in which one population was tagged with a fluorescent marker to monitor heterotypi c channel activity. The cotransfected cells possessed channel types un like the homotypic forms of rCx43 or hCx37 or the heterotypic forms. I n addition, the noninstantaneous transjunctional conductance-transjunc tional voltage (G(j)/V-j) relationship for cotransfected cell pairs sh owed a large range of variability that was unlike that-of the homotypi c or heterotypic form. The heterotypic cell pairs displayed asymmetric voltage dependence. The results from the heteromeric cell pairs are i nconsistent with summed behavior of two independent homotypic populati ons or mixed populations of homotypic and heterotypic channels types. The G(j)/V-j data imply that the connexin-to-connexin interactions are significantly altered in cotransfected cell pairs relative to the hom otypic and heterotypic forms. Heteromeric channels are a population of channels whose characteristics could well impact differently from the ir homotypic counterparts with regard to multicellular coordinated res ponses.