Coexpression of connexin 45 with connexin 43 decreases gap junction size.
In the human heart, ventricular myocytes express connexin 43 (Cx43) and traces of Cx45. In congestive heart failure, Cx43 levels decrease, Cx45 levels increase and gap junction size decreases. To determine whether alterations of connexin coexpression ratio influence gap junction size, we engineered a rat liver epithelial cell line that endogenously expresses Cx43 to coexpress inducible levels of Cx45 under stimulation of the insect hormone, ponasterone A. In cells induced to express Cx45, gap junction sizes are significantly reduced (by 15% to 20%; p < 0.001), an effect that occurs despite increased levels of junctional connexons made from both connexins. In contrast, coexpression of Cx40 with Cx43 does not lead to any change in gap junction size. These results are consistent with the idea that increased Cx45 expression in the failing ventricle contributes to decreased gap junction size.
Grikscheit
Katharina
K
Department of Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom.
Thomas
Neil
N
Bruce
Alexandra F
AF
Rothery
Stephen
S
Chan
Joachim
J
Severs
Nicholas J
NJ
Dupont
Emmanuel
E
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics*; D017630:Connexins / Q000096:biosynthesis / Q000235:genetics*; D017629:Gap Junctions / Q000378:metabolism*; D006367:HeLa Cells; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats
D018031:Connexin 43; D017630:Connexins; C082920:connexin 45