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The participation of the Na + –Ca 2+ exchanger in primary cardiac myofibroblast migration, contraction, and proliferation
Author(s) -
Raizman Joshua E.,
Komljenovic Jelena,
Chang Rose,
Deng Cicie,
Bedosky Kristen M.,
Rattan Sunil G.,
Cunnington Ryan H.,
Freed Darren H.,
Dixon Ian M.C.
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21134
Subject(s) - myofibroblast , motility , myosin , rhoa , microbiology and biotechnology , myocyte , contraction (grammar) , downregulation and upregulation , chemistry , biology , medicine , endocrinology , signal transduction , biochemistry , fibrosis , gene
Cardiac ventricular myofibroblast motility, proliferation, and contraction contribute to post‐myocardial infarct wound healing, infarct scar formation, and remodeling of the ventricle remote to the site of infarction. The Na + –Ca 2+ exchanger (NCX1) is involved in altered calcium handling in cardiac myocytes during cardiac remodeling associated with heart failure, however, its role in cardiac myofibroblast cell function is unexplored. In this study we investigated the involvement of NCX1 as well as the role of non‐selective‐cation channels (NSCC) in cardiac myofibroblast cell function in vitro. Immunofluorescence and Western blots revealed that P1 cells upregulate α‐smooth muscle actin (αSMA) and embryonic smooth muscle myosin heavy chain (SMemb) expression. NCX1 mRNA and proteins as well as Ca v 1.2a protein are also expressed in P1 myofibroblasts. Myofibroblast motility in the presence of 50 ng/ml PDGF‐BB was blocked with AG1296. Myofibroblast motility, contraction, and proliferation were sensitive to KB‐R7943, a specific NCX1 reverse‐mode inhibitor. In contrast, only proliferation and contraction, but not motility were sensitive to nifedipine, while gadolinium (NSCC blocker) was only associated with decreased motility. ML‐7 treatment was associated with inhibition of the chemotactic response and contraction. Thus cardiac myofibroblast chemotaxis, contraction, and proliferation were sensitive to different pharmacologic treatments suggesting that regulation of transplasmalemmal calcium movements may be important in growth factor receptor‐mediated processes. NCX1 may represent an important moiety in suppression of myofibroblast functions. J. Cell. Physiol. 213: 540–551, 2007. © 2007 Wiley‐Liss, Inc.