Gap junctions are plasma membrane domains of intercellular channels that allow direct connection between the cytoplasm of adjacent cells. They allow exchange of low molecular weight metabolites, ions and small hydrophilic molecules. These channels are formed by head-to-head docking of hexameric hemichannels called connexons, whose subunit proteins are encoded by the connexin (Cx) gene family^1-3.

The connexin subunit is formed of four-transmembrane spanning domains, harboring two extracellular loops, one cytoplasmic loop and cytoplasmic N- and C-terminal regions. To date, the family of connexin comprises 21 genes in the human genome⁴.

Connexin 45 (Cx45), encoded by the GJC1 gene, is expressed in cardiomyocytes and in developing vasculature in both endothelial and smooth muscle cells^4,5.

In the heart, Cx45 along with Cx40 and Cx43, play a crucial role in normal electrical conduction and synchronous heart muscle contraction and important for the normal embryonic development of the heart⁶. Indeed Cx45 forms low conductance and voltage-sensitive gap junctions between the ventricular cardiac myocytes and the core conduction system². 

Studies have showed that cardiac connexin Cx45 is upregulated in human failing hearts and has an important role in the regulation of endothelial-induced mural cell differentiation^4,5_.