Alterations of intercellular communication in neonatal cardiac myocytes from connexin43 null mice

doi:10.1016/j.cardiores.2004.01.015

Cardiovascular Research 2004 62(2):397-406; doi:10.1016/j.cardiores.2004.01.015
© 2004 by European Society of Cardiology

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Alterations of intercellular communication in neonatal cardiac myocytes from connexin43 null mice

Monique J Vink^a, Sylvia O Suadicani^a, Delia M Vieira^b, Marcia Urban-Maldonado^a, Yang Gao^a, Glenn I Fishman^b^,c and David C Spray^*^,a^,b

^aDepartment of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
^bDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
^cThe Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY 10016, USA

^* Corresponding author. Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Tel.: +1-718-430-2537; fax: +1-718-430-8594. Email address: spray{at}aecom.yu.edu

Objective: To compare gap junction expression and intercellularcoupling in wildtype neonatal cardiac myocytes to those frommice lacking the most abundant cardiac gap junction protein(connexin43, Cx43). Methods: Northern and Western blots comparedconnexin mRNA and protein levels, immunocytochemistry evaluatedconnexin distribution in neonatal Cx43 null(–/–),heterozygous(+/–) and wildtype(+/+) mouse hearts. Ca²⁺imaging, dye coupling and electrophysiological methods evaluatedintercellular communication. Results: Similar levels of Cx40and Cx45 were detected in all genotypes, although in adult cardiactissue from wildtype mice, Cx43 expression was higher than inheterozygotes. After culturing dissociated cells for 3–4days, cardiocytes beat spontaneously; in Cx43(+/+) and (+/–)cultures, the beating was generally quite synchronous. In Cx43(–/–)mice, interbeat intervals were on average twice as long andmore variable than in Cx43(+/+) or Cx43(+/–) cultures.Junctional conductance was lower by about 60% in Cx43(–/–)as compared to Cx43(+/–) and (+/+) littermates; LuciferYellow dye coupling was virtually absent in Cx43(–/–)cardiomyocytes but was comparably strong in wildtype and heterozygoussiblings. Macroscopic junctional conductance measurements onCx43(–/–) cardiocytes showed slightly stronger voltagesensitivity in these cells than in Cx43(+/+) cardiocytes. Unitaryjunctional conductance measurements revealed distinct populationsof channels contributing to macroscopic conductance for Cx43(+/+)and Cx43(–/–) genotypes. Conclusions: In Cx43-deficientcardiac myocytes, the expression of other connexins only partiallycompensates for the functional loss, with dye coupling and spontaneousbeating being strongly impaired.

KEYWORDS Gap junction; Nexus; Electrical coupling; Arrhythmia; Knockout mice; Cx43

Time for primary review 31 days

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