Cell transplantation of skeletal myoblasts (SMs) is one possible treatment for repairing cardiac tissue after myocardial injury. However, inappropriate electrical coupling between grafted SMs and host cardiomyocytes may be responsible for the arrhythmias observed in clinical trials of SM transplantation. Whether functional gap junctions occur between the two cell types remains controversial. We have studied the ability of SMs to electrically couple with isolated adult rat cardiomyocytes (CMs) and assessed whether connexin43 (Cx43) overexpression enhanced gap junctional conductance (G_j). C₂C₁₂ myoblast lines overexpressing Cx43 were generated by gene transfection and clonal selection. CMs were cocultured with either SMs overexpressing Cx43 (CM-SM^Cx43) or control SMs (CM-SM^WT) in vitro. G_j between pairs of SMs and CMs was quantified with dual whole cell patch clamping. Formation of G_j occurred between 22% of CM-SM^WT pairs (n=73) and 48% of CM-SM^Cx43 pairs (n=71, P<0.001). The G_j of CM-SM^Cx43 pairs (29.7±4.3 nS, n=21) was greater than that of CM-SM^WT pairs (14.8±2.0 nS, n=12, P<0.05). The overexpression of Cx43 in SMs increased the formation of electrical communication and the steady-state conductance between SMs and CMs. Enhanced gap junctional conductance may be useful to promote the integration of transplanted SMs into the myocardium.

Key words: gap junctional conductance • electrophysiology