Molecular Cloning of Two Human Cardiac Gap Junction Proteins, Connexin40 and Connexin45

Intercellular coupling of cardiac myocytes through gap junction channels facilitates normal cardiac impulse conduction. Multiple gap junction sequences (connexins) have been previously identified in mammalian and avian heart, but only one, connexin43 (Cx43), has been identified in the human heart. We used the polymerase chain reaction and genomic cloning to isolate DNA encoding the gap junction proteins human connexin40 (Cx40) and connexin45 (Cx45). Northern blots showed that specific probes for Cx43, Cx40 and Cx45 all hybridize to distinct mRNAs in human ventricular RNA. Immunohistochemistry with connexin-specific antibodies confirmed that Cx40, Cx43, and Cx45 all localized to intercalated disk regions in frozen sections of human left ventricle. The presence of multiple connexins in human ventricle may contribute to divergent mechanisms of regulation of cardiac conduction.