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Cardiac myocyte‐specific caveolin‐3 overexpression alters β‐adrenergic receptor activity
Author(s) -
Busija Anna Rebecca,
Roth David M.,
Insel Paul A.,
Patel Hemal H.
Publication year - 2012
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.26.1_supplement.1114.18
Subject(s) - caveolae , caveolin 3 , myocyte , caveolin , agonist , medicine , endocrinology , receptor , microbiology and biotechnology , cardiac myocyte , chemistry , cardiac function curve , adrenergic , biology , heart failure , signal transduction
Caveolins are scaffolding proteins essential to the formation of caveolae, plasma membrane invaginations that compartmentalize signaling molecules. Mice with cardiac myocyte‐specific overexpression of caveolin‐3 (Cav‐3 OE) have increased caveolae number in cardiac myocytes and are protected from ischemia‐reperfusion injury, while mice lacking Cav‐3 (Cav‐3 KO) lack cardiac caveolae and are more sensitive to cardiac injury. β‐adrenergic receptors (β‐ARs) localize to caveolae and when stimulated by agonists alter cardiac inotropy and chronotropy but whether increased Cav‐3 expression alters β‐AR agonist response in the heart is unknown. We treated Langendorff‐perfused hearts from transgene‐negative (TGneg), Cav‐3 KO, and Cav‐3 OE mice with the β‐AR agonist isoproterenol (Iso). Cav‐3 OE mice had augmented Iso‐stimulated inotropy (+dP/dt) and lusitropy (−dP/dt) relative to TGneg mice but response was reduced in Cav‐3 KO mice. Cardiac myocytes (CM) isolated from Cav‐3 OE mice had enhanced Iso‐stimulated production of cAMP while Cav‐3 KO CM had reduced cAMP production. These data indicate that the expression of Cav‐3 is a key modifier of β‐AR‐promoted cAMP formation and contractile function. Physiological or pathological alteration in Cav‐3 expression thus has the potential to modulate cardiac response to sympathetic activation. Research supported by VMIRF and NIH research grants.