Chamber-related differences in connexin expression in the human heart

Electrical coupling in the heart is mediated by gap junctions, aggregates o f cell-to-cell channels composed of connexins. The principal cardiac gap-ju nctional connexin, connexin43 (Cx43), is reduced in diseased human myocardi um that is prone to arrhythmia. Three additional connexin isoforms, Cx40, C x45 and Cx37, of distinctive functional capacities in vitro, are expressed in cardiovascular cells, but our knowledge of their expression patterns in the human heart is fragmentary. In the present study, we therefore applied Northern blotting. Western blotting and immunoconfocal microscopy to analys e and compare the expression of Cx43, Cx40, Cx37 and Cx45 mRNA and protein in the human left ventricle, right ventricle, left atrium and right atrium of the human heart. Cx43 was confirmed to be abundantly expressed at simila r levels by myocytes in all four chambers, Cx40 levels varied between chamb ers in the order right atrium >left atrium >>right ventricle congruent to l eft ventricle. Cx37 (exclusively expressed in the endothelium) was expresse d at similar overall levels in all chambers (as judged from Northern blots) . Cx45 was detectable only at very low levels, with a trend toward higher l evels in the atria than the ventricles in a pattern similar to Cx40. The re sults indicate that in humans. the Ventricles and atria have distinctive co nnexin expression profiles, and that the atrial-type connexin profile is mo re pronounced in the right atrium than the left atrium, While the ventricul ar connexin expression pattern resembles that of other mammalian species, a trial connexin expression shows greater species variation. These difference s contribute to the interpretative framework for examining the potential ro le of altered connexin expression in ventricular and atrial arrhythmia in t he human heart. (C) 1999 Academic Press.