Heterogeneous expression of gap junction channels in the heart leads to conduction defects and ventricular dysfunction

David E. Gutstein, Gregory E. Morley, Dhananjay Vaidya, Fangyu Liu, Franklin L. Chen, Heidi Stuhlmann, Glenn I. Fishman

Research output: Contribution to journalArticle

Abstract

Background - Heterogeneous remodeling of gap junctions is observed in many forms of heart disease. The consequent loss of synchronous ventricular activation has been hypothesized to result in diminished cardiac performance. To directly test this hypothesis, we designed a murine model of heterogeneous gap junction channel expression. Methods and Results - We generated chimeric mice formed from connexin43 (Cx43)-deficient embryonic stem cells and wild-type or genetically marked ROSA26 recipient blastocysts. Chimeric mice developed normally, without histological evidence of myocardial fibrosis or hypertrophy. Heterogeneous Cx43 expression resulted in conduction defects, however, as well as markedly depressed contractile function. Optical mapping of chimeric hearts by use of voltage-sensitive dyes revealed highly irregular epicardial conduction patterns, quantified as significantly greater negative curvature of the activation wave front (-1.86±0.40 mm in chimeric mice versus -0.86±0.098 mm in controls; P

Original languageEnglish (US)
Pages (from-to)1194-1199
Number of pages6
JournalCirculation
Volume104
Issue number10
StatePublished - Sep 4 2001

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Ventricular Dysfunction
Gap Junctions
Connexin 43
Blastocyst
Embryonic Stem Cells
Hypertrophy
Heart Diseases
Fibrosis
Coloring Agents

Keywords

  • Arrhythmia
  • Conduction
  • Contractility
  • Genes
  • Ion channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Gutstein, D. E., Morley, G. E., Vaidya, D., Liu, F., Chen, F. L., Stuhlmann, H., & Fishman, G. I. (2001). Heterogeneous expression of gap junction channels in the heart leads to conduction defects and ventricular dysfunction. Circulation, 104(10), 1194-1199.

Heterogeneous expression of gap junction channels in the heart leads to conduction defects and ventricular dysfunction. / Gutstein, David E.; Morley, Gregory E.; Vaidya, Dhananjay; Liu, Fangyu; Chen, Franklin L.; Stuhlmann, Heidi; Fishman, Glenn I.

In: Circulation, Vol. 104, No. 10, 04.09.2001, p. 1194-1199.

Research output: Contribution to journalArticle

Gutstein, DE, Morley, GE, Vaidya, D, Liu, F, Chen, FL, Stuhlmann, H & Fishman, GI 2001, 'Heterogeneous expression of gap junction channels in the heart leads to conduction defects and ventricular dysfunction', Circulation, vol. 104, no. 10, pp. 1194-1199.
Gutstein, David E. ; Morley, Gregory E. ; Vaidya, Dhananjay ; Liu, Fangyu ; Chen, Franklin L. ; Stuhlmann, Heidi ; Fishman, Glenn I. / Heterogeneous expression of gap junction channels in the heart leads to conduction defects and ventricular dysfunction. In: Circulation. 2001 ; Vol. 104, No. 10. pp. 1194-1199.
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