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Caveolin‐3 Regulation of Cardiac Contractile Function is Facilitated by Enhanced Mitochondrial Efficiency
Author(s) -
Busija Anna R.,
Schilling Jan M.,
Roth David M.,
Insel Paul A.,
Patel Hemal H.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1197.4
Subject(s) - caveolae , caveolin 3 , microbiology and biotechnology , mitochondrion , myocyte , reactive oxygen species , cardiac function curve , chemistry , receptor , medicine , endocrinology , biology , signal transduction , heart failure , biochemistry
Caveolins (Cavs) are scaffolding proteins integral to caveolae, membrane lipid raft domains that compartmentalize numerous proteins and signaling molecules, including β‐adrenergic receptors (β‐ARs). Mice with cardiac myocyte (CM)‐specific overexpression of Cav‐3 (Cav‐3 OE) have more caveolae in CMs and are protected from ischemia‐reperfusion injury. Here, we tested the hypothesis that increases in Cav‐3 expression in CMs may alter β‐AR response, especially since data from our laboratory have shown mitochondria from Cav‐3 OE hearts are resistant to calcium loading and generate fewer reactive oxygen species. We reasoned that Cav‐3 OE, by compartmentation of interdependent signaling components of the β‐AR response in close approximation to mitochondria, may change responses to β‐AR activation. Cav‐3 OE hearts treated with the β‐AR agonist isoproterenol (Iso) have augmented inotropy (+dP/dt) and lusitropy (−dP/dt) compared to transgene negative hearts. CMs isolated from Cav‐3 OE mice have a 2‐fold increase in maximal Iso‐promoted cAMP production. However, isolated Cav‐3 OE CMs incubated with Iso show only a small increase in mitochondrial respiration. Thus, increased expression of Cav‐3 enhances Iso‐mediated positive inotropy without a proportional increase in mitochondrial respiration. We conclude that increased expression of Cav‐3 enhances cardiac function by enhancing responsivity of the heart and increasing mitochondrial oxygen efficiency in response to βAR stimuli, thus identifying an increase in Cav‐3 as a novel means to increase cardiac function in a manner that may not require increased oxygen consumption. Support or Funding Information NIH HL107200, AHA 14PRE20460372.