Gap junctional connexins in the developing mouse cardiac conduction system.

Gap junctional channels which couple myocytes mediate conduction phenomena in the heart. These channels are dodecamers of transmembrane proteins belonging to the connexin family (Cx). Three Cxs, Cx43, -40 and -45, have been found to be expressed in cardiomyocytes. Each of them has a distinct spatiotemporal pattern of expression, which is regulated during development. In the adult mouse heart, Cx43 is expressed in all the working myocytes and most of the conductive myocytes; Cx45 is weakly expressed in all conductive myocytes, including those of the nodal tissues; Cx40 expression is restricted to the atria and ventricular conduction system. Analysis of mice with deletions of Cx genes has provided evidence that Cx43, -40 and -45, and consequently the gap junctional channels they form, are involved in both heart function and development. For example, Cx40 deficiency results in sinoatrial conduction impairments, a significant decrease of the conduction velocity in the atria, and a delay of the propagation of impulse in the His bundle. Transgenic mouse lines with modified Cx40 genes are now being used to draw up a detailed map of the conduction system in the adult and developing heart, and to identify the regulatory elements involved in the transcriptional regulation of the Cx40 gene. Some preliminary results of these studies are described.