Evidence for heteromeric gap junction channels formed from rat connexin43 and human connexin37

P. R. Brink, K. Cronin, K. Banach, E. Peterson, E. M. Westphale, K. H. Seul, S. V. Ramanan, E. C. Beyer
1997 American Journal of Physiology - Cell Physiology  
Evidence for heteromeric gap junction channels formed from rat connexin43 and human connexin37. Am. J. Physiol. 273 (Cell Physiol. 42): C1386-C1396, 1997.-Homomeric gap junction channels are composed solely of one connexin type, whereas heterotypic forms contain two homomeric hemichannels but the six identical connexins of each are different from each other. A heteromeric gap junction channel is one that contains different connexins within either or both hemichannels. The existence of
more » ... stence of heteromeric forms has been suggested, and many cell types are known to coexpress connexins. To determine if coexpressed connexins would form heteromers, we cotransfected rat connexin43 (rCx43) and human con-nexin37 (hCx37) into a cell line normally devoid of any connexin expression and used dual whole cell patch clamp to compare the observed gap junction channel activity 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 heterotypic channel activity. The cotransfected cells possessed channel types unlike the homotypic forms of rCx43 or hCx37 or the heterotypic forms. In addition, the noninstantaneous transjunctional conductance-transjunctional voltage (G j /V j ) relationship for cotransfected cell pairs showed a large range of variability that was unlike that of the homotypic or heterotypic form. The heterotypic cell pairs displayed asymmetric voltage dependence. The results from the heteromeric cell pairs are inconsistent with summed behavior of two independent homotypic populations 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 homotypic and heterotypic forms. Heteromeric channels are a population of channels whose characteristics could well impact differently from their homotypic counterparts with regard to multicellular coordinated responses. homotypic channels; heteromeric channels; heterotypic channels; voltage gating GAP JUNCTION CHANNELS provide an intercellular pathway between adjacent cells for ions and small solutes such as second messenger molecules. Unlike other ion channels, the gap junction channel consists of two hemichannels or connexons, each contributed by one of two adjacent cells. Hemichannels are oligomers, formed by six protein subunits called connexins. Connexins belong to a gene family with 13 identified members (3). On the basis of hydropathic studies, the connexins are predicted to have four transmembrane domains, with the amino and the carboxy termini located on the cytoplasmic side. Adjacent cells can synthesize the
doi:10.1152/ajpcell.1997.273.4.c1386 fatcat:lgjp6v5ilnhv7c6u4u53yjfwq4