Transcriptional control of myocardial connexins

Rapid spreading of the electrical impulse throughout the heart is essential for coordinated contraction and is mediated by electrical coupling of cardiomyocytes through gap junction channels composed of connexin40 (Cx40), connexin43 (Cx43) or connexin45 (Cx45). Each of these connexin proteins has a characteristic developmental and regional expression pattern in the heart. Alterations in this pattern may result in abnormal cellular coupling and consequently contribute to irregularities in cardiac rhythm. Indeed, alterations in cardiac connexin expression have been correlated with cardiovascular disease for which the molecular mechanisms, however, are largely unknown. Transcription factors and their target elements in the genome regulate the expression of genes during development and in response to extracellular signals in a cell type-specific and quantitative manner. Altered transcriptional regulation of gene expression is a characteristic feature in the development of cardiac disease which may influence the connexin expression pattern as well. In this review, we will summarize what is known on transcriptional regulation of the Cx40, Cx43 and Cx45 genes in general, with an emphasis on the heart.