Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy

Joseph J. Gard, Kiyomi Yamada, Karen G. Green, Benjamin C. Eloff, David S. Rosenbaum, Xuejun Wang, Jeffrey Robbins, Richard B. Schuessler, Kathryn A. Yamada, Jeffrey E. Saffitz

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Objective: We studied a transgenic mouse model of human desmin-related cardiomyopathy with cardiac-specific expression of a 7-amino acid deletion mutation in desmin (D7-des) to test the hypothesis that impaired linkage between desmin and desmosomes alters expression and function of the electrical coupling protein, connexin43 (Cx43). Methods: Expression of Cx43 and selected mechanical junctions proteins was characterized in left ventrices of D7-des and control mice by quantitative confocal microscopy and immunoblotting. Remodeling of gap junctions was also analyzed by electron microscopic morphometry. The electrophysiological phentoype of D7-des mice was characterized by electrocardiography and optical mapping of transmembrane voltage. Results: Cx43 signal at intercalated disks was decreased by ∼3-fold in D7-des ventricular tissue due to reductions in both gap junction number and size. Immunoreactive signal at cell-cell junctions was also reduced significantly for adhesion molecules and linker proteins of desmosomes and fascia adherens junctions. Electron microscopy showed decreased gap junction remodeling. However, immunoblotting showed that the total tissue content of Cx43 and mechanical junction proteins was not reduced, suggesting that diminished signal at cell-cell junctions was not due to insufficient protein expression, but to failure of these proteins to assemble properly within electrical and mechanical junctions. Remodeling of gap junctions in D7-des mice led to slowing of ventricular conduction as demonstrated by optical electrophysiological mapping. Conclusions: These results illustrate how a defect in a protein conventionally thought to fulfill a mechanical function in the heart can also lead to electrophysiological alterations that may contribute to arrhythmogenesis.

Original languageEnglish (US)
Pages (from-to)539-547
Number of pages9
JournalCardiovascular research
Volume67
Issue number3
DOIs
StatePublished - Aug 15 2005

Fingerprint

Desmin
Gap Junctions
Cardiomyopathies
Connexin 43
Proteins
Desmosomes
Intercellular Junctions
Immunoblotting
Adherens Junctions
Sequence Deletion
Fascia
Confocal Microscopy
Transgenic Mice
Electron Microscopy
Electrocardiography
Electrons
Amino Acids

Keywords

  • Cardiomyopathy
  • Cell communication
  • Cytoskeleton
  • Gap junctions

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Gard, J. J., Yamada, K., Green, K. G., Eloff, B. C., Rosenbaum, D. S., Wang, X., ... Saffitz, J. E. (2005). Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy. Cardiovascular research, 67(3), 539-547. https://doi.org/10.1016/j.cardiores.2005.04.004

Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy. / Gard, Joseph J.; Yamada, Kiyomi; Green, Karen G.; Eloff, Benjamin C.; Rosenbaum, David S.; Wang, Xuejun; Robbins, Jeffrey; Schuessler, Richard B.; Yamada, Kathryn A.; Saffitz, Jeffrey E.

In: Cardiovascular research, Vol. 67, No. 3, 15.08.2005, p. 539-547.

Research output: Contribution to journalArticle

Gard, JJ, Yamada, K, Green, KG, Eloff, BC, Rosenbaum, DS, Wang, X, Robbins, J, Schuessler, RB, Yamada, KA & Saffitz, JE 2005, 'Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy', Cardiovascular research, vol. 67, no. 3, pp. 539-547. https://doi.org/10.1016/j.cardiores.2005.04.004
Gard, Joseph J. ; Yamada, Kiyomi ; Green, Karen G. ; Eloff, Benjamin C. ; Rosenbaum, David S. ; Wang, Xuejun ; Robbins, Jeffrey ; Schuessler, Richard B. ; Yamada, Kathryn A. ; Saffitz, Jeffrey E. / Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy. In: Cardiovascular research. 2005 ; Vol. 67, No. 3. pp. 539-547.
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AU - Rosenbaum, David S.

AU - Wang, Xuejun

AU - Robbins, Jeffrey

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