Mono-Heteromeric Configurations of Gap Junction Channels Formed by Connexin43 and Connexin45 Reduce Unitary Conductance and Determine both Voltage Gating and Metabolic Flux Asymmetry

摘要: In cardiac tissues, the expression of multiple connexins (Cx40, Cx43, Cx45 and Cx30.2) is a requirement for proper development function. Gap junctions formed by these have distinct permeability gating mechanisms. Since single cell can express more than one connexin isoform, formation hetero-multimeric gap junction channels provides tissue with an enormous repertoire combinations to modulate intercellular communication. To study further perm-selectivity properties containing Cx43 Cx45, we studied two monoheteromeric in which HeLa co-transfected was paired expressing only connexins. Macroscopic measurements total conductance between pairs indicated drastic reduction mono-heteromeric channels. terms Vj dependent gating, homomeric connexons facing heteromeric responded weakly voltage negativity. exhibited no change when connexons. The distributions unitary conductances (j) both were smaller predicted, showed low fluorescent dyes Lucifer yellow Rhodamine123. For channels, observed flux asymmetry regardless dye charge: higher direction connexon MhetCx45 MhetCx43. Thus, our data suggest that co-expression induces greatly reduced conductance. Furthermore, it increases opposing connexons, favors asymmetric molecules across depends primarily on size (not charge) crossing molecules.