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This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/H806    most recent 01058.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bupha-Intr, T. Articles by Janssen, P. M. L. Search for Related Content PubMed PubMed Citation Articles by Bupha-Intr, T. Articles by Janssen, P. M. L.

Temporal changes in expression of connexin 43 after load-induced hypertrophy in vitro

¹Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio; and ²Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand

Submitted 3 October 2008 ; accepted in final form 5 January 2009

Upon remodeling of the ventricle after a provoking stimulus, such as hypertension, connections between adjacent myocytes may need to be "reformatted" to preserve a synchronization of excitation of the remodeling heart. In the mammalian heart, the protein connexin forms the gap junctions that allow electrical and chemical signaling communication between neighboring cells. We aim to elucidate whether mechanical load, in isolation, potentially changes the expression of connexin 43 (Cx43), the major isoform of the connexin family in the ventricle, and its phosphorylation. Cx43 expression levels and contractile function of multicellular rabbit cardiac preparations were assessed in a newly developed in vitro system that allows for the study of the transition of healthy multicellular rabbit myocardium to hypertrophied myocardium. We found that in mechanically loaded cardiac trabeculae, Cx43 levels remained stable for about 12 h and then rapidly declined. Phosphorylation at Ser368 declined much faster, being almost absent after 2 h of high-load conditions. No-load conditions did not affect Cx43 levels, nor did phosphorylation at Ser368. The downregulation of Cx43 under mechanical load did not correspond with the contractile changes that were observed. Furthermore, blocking paracrine activity of the muscle could only partially prevent the downregulation of Cx43. Additionally, no effect of mechanical loading on the expression of N-cadherin and zonula occludens-1 was observed, indicating a specificity of the connexin response. High mechanical load induced a rapid loss of Cx43 phosphorylation, followed by a decrease in Cx43 protein levels. Paracrine factors are partly responsible for the underlying mechanism of action, whereas no direct correlation to contractile ability was observed.

contractility; gap junction; rabbit; trabeculae