Cardiac-restricted inactivation of connexin43 in mice severely reduced junctional coupling to 4-11 nS compared to 558-588 nS in controls, suggesting additional mechanisms maintain in vivo conduction.
Mice with cardiac-restricted inactivation of the connexin43 gene (CKO mice) have moderate slowing of ventricular conduction and lethal arrhythmias. Mechanisms through which propagation is maintained in the absence of Cx43 are unknown. We evaluated gap junctional conductance in CKO ventricular pairs using dual patch clamp methods. Junctional coupling was reduced to 4+/-2 nS (side-to-side) and 11+/-2 nS (end-to-end), including 21% of cell-pairs with no detectable coupling, compared with 588+/-104 nS (side-to-side) and 558+/-92 nS (end-to-end) in control cell-pairs. Voltage dependence of control gap junctions was characteristic of Cx43. CKO conductance showed increased voltage dependence, suggesting low-level expression of other connexin isoforms. From theoretical models, this degree of CKO coupling is not expected to support levels of conduction persisting in vivo, suggesting the possibility that there are additional mechanisms for maintained propagation when gap junctional conductance is severely reduced.
Yao et al. (Tue,) conducted a other in Connexin43-deficient murine hearts. Cardiac-restricted inactivation of the connexin43 gene vs. Control cell-pairs was evaluated on Gap junctional conductance in ventricular pairs. Cardiac-restricted inactivation of connexin43 in mice severely reduced junctional coupling to 4-11 nS compared to 558-588 nS in controls, suggesting additional mechanisms maintain in vivo conduction.