Dataset Information

Connexin43 ablation in foetal atrial myocytes decreases electrical coupling, partner connexins, and sodium current.

ABSTRACT:

Aims

Remodelling and regional gradients in expression of connexins (Cx) are thought to contribute to atrial electrical dysfunction and atrial fibrillation. We assessed the effect of interaction between Cx43, Cx40, and Cx45 on atrial cell-to-cell coupling and inward Na current (I(Na)) in engineered pairs of atrial myocytes derived from wild-type mice (Cx43(+/+)) and mice with genetic ablation of Cx43 (Cx43(-/-)).

Methods and results

Cell pairs were engineered by microcontact printing from atrial Cx43(+/+) and Cx43(-/-) murine myocytes (1 day before birth, 3-5 days in culture). Dual and single voltage clamp were used to measure intercellular electrical conductance, g(j), and its dependence on transjunctional voltage, V(j), single gap junction channel conductances, and I(Na). 3D reconstructions of Cx43, Cx40, and Cx45 immunosignals in gap junctions were made from confocal slices. Full genetic Cx43 ablation produced a decrease in immunosignals of Cx40 to 62 ± 10% (mean ± SE; n= 17) and Cx45 to 66 ± 8% (n= 16). G(j) decreased from 80 ± 9 nS (Cx43(+/+), n= 17) to 24 ± 2 nS (Cx43(-/-), n= 35). Single channel analysis showed a shift in the main peak of the channel histogram from 49 ± 1.7 nS (Cx43(+/+)) to 67 ± 1.8 nS (Cx43(-/-)) with a second minor peak appearing at 27 ± 1.5 pS. The dependence of g(j) on V(j) decreased with Cx43 ablation. Importantly, peak I(Na) decreased from -350 ± 44 pA/pF (Cx43(+/+)) to -154 ± 28 pA/pF (Cx43(-/-)).

Conclusions

The dependence of Cx40, Cx45, and I(Na) on Cx43 expression indicates a complex interaction between connexins and I(Na) in the atrial intercalated discs that is likely to be of relevance for arrhythmogenesis.

SUBMITTER: Desplantez T

PROVIDER: S-EPMC3307380 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Publications

Connexin43 ablation in foetal atrial myocytes decreases electrical coupling, partner connexins, and sodium current.

Desplantez Thomas T McCain Megan L ML Beauchamp Philippe P Rigoli Ghislaine G Rothen-Rutishauser Barbara B Parker Kevin Kit KK Kleber Andre G AG

Cardiovascular research 20120127 1

<h4>Aims</h4>Remodelling and regional gradients in expression of connexins (Cx) are thought to contribute to atrial electrical dysfunction and atrial fibrillation. We assessed the effect of interaction between Cx43, Cx40, and Cx45 on atrial cell-to-cell coupling and inward Na current (I(Na)) in engineered pairs of atrial myocytes derived from wild-type mice (Cx43(+/+)) and mice with genetic ablation of Cx43 (Cx43(-/-)).<h4>Methods and results</h4>Cell pairs were engineered by microcontact printi ...[more]

PMID: 22287588

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Dataset Information

Connexin43 ablation in foetal atrial myocytes decreases electrical coupling, partner connexins, and sodium current.

Aims

Methods and results

Conclusions

Publications

Connexin43 ablation in foetal atrial myocytes decreases electrical coupling, partner connexins, and sodium current.

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