While ventricular gap junctions contain only Cx43, atrial gap junctions contain both Cx40 and Cx43; yet the functional consequences of this co-expression remain poorly understood. We quantitated the expression of Cx40 and Cx43 and their contributions to atrial gap junctional conductance (gj). Neonatal murine atrial myocytes showed similar abundances of Cx40 and Cx43 proteins, while ventricular myocytes contained at least 20 times more Cx43 than Cx40. Since Cx40 gap junction channels are blocked by 2 mM spermine while Cx43 channels are unaffected, we used spermine block as a functional dual whole cell patch clamp assay to determine Cx40 contributions to cardiac gj. Slightly more than half of atrial gj and ≤ 20% of ventricular gj were inhibited. In myocytes from Cx40 null mice, the inhibition of ventricular gj was completely abolished, and the block of atrial gj was reduced to < 20%. Compared to ventricular gap junctions, the transjunctional voltage (Vj)-dependent inactivation of atrial gj was reduced and kinetically slowed, while the Vj-dependence of fast and slow inactivation was unchanged. We conclude that Cx40 and Cx43 are equally abundant in atrium and make similar contributions to atrial gj. Co-expression of Cx40 accounts for most, but not all, of the differences in the Vj-dependent gating properties between atrium and ventricle that may play a role in the genesis of slow myocardial conduction and arrhythmias.
- Gap junctions