Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cardiovasc Res. 2010 Mar 1;85(4):751-62. doi: 10.1093/cvr/cvp353. Epub 2009 Oct 30.

Connexin43 knockdown or overexpression modulates cell coupling in control and failing rabbit left ventricular myocytes.

Author information

  • 1Division of Cardiovascular Disease, Department of Medicine, UAB Center for Cardiovascular Biology, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall B140, Birmingham, AL 35294, USA. xai@uab.edu

Abstract

AIMS:

We have shown that failing human and rabbit left ventricle (LV) exhibits downregulation and dephosphorylation of connexin43 (Cx43) and that Cx43 dephosphorylation in heart failure (HF) contributes to reduced cell coupling. However, the role of Cx43 downregulation per se in impaired coupling in HF is unclear.

METHODS AND RESULTS:

First, we used adenovirus (Ad) encoding a Cx43 siRNA sequence to knock down Cx43 protein levels in cultured control rabbit LV myocytes. Cells cultured for up to 48 h with intermittent pacing maintained Cx43 protein levels and phosphorylation status. Cell coupling in Cx43 knockdown myocyte pairs (by Lucifer Yellow dye transfer) was markedly reduced after 24 h infection (associated with approximately 40% Cx43 knockdown) and after 48 h (associated with approximately 70% Cx43 knockdown). The phosphorylation status, distribution of remaining Cx43 proteins, and levels of other cardiac connexins (Cx40 and Cx45) were unchanged. Second, we overexpressed Cx43 to levels comparable to control using an adenovirus encoding wild-type Cx43 (Cx43WT) gene in isolated LV myocytes from our arrhythmogenic HF rabbit model. We found 87% more Cx43WT proteins improved dye coupling [vs. Ad-beta-galactosidase (LacZ) infected HF controls]. Overexpressed Cx43 protein was located throughout the myocyte membrane (same pattern as in controls), and the phosphorylation status of Cx43 remained comparable to that in AdLacZ infected HF controls.

CONCLUSION:

In addition to Cx43 dephosphorylation, downregulation of Cx43 plays an essential role in reduced cell coupling in the failing rabbit heart. Modulation of Cx43 expression could be a novel therapeutic approach to improve conduction and decrease sudden death in HF.

PMID:
19880431
[PubMed - indexed for MEDLINE]
PMCID:
PMC2860702
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk