title: Caveolae-localized L-type Ca2+ channels do not contribute to function or hypertrophic signalling in the mouse heart.
abstract: OBJECTIVE
  L-type Ca2+ channels (LTCCs) in adult cardiomyocytes are localized to t-tubules where they initiate excitation-contraction coupling. Our recent work has shown that a subpopulation of LTCCs found at the surface sarcolemma in caveolae of adult feline cardiomyocytes can also generate a Ca2+ microdomain that activates nuclear factor of activated T-cells signaling and cardiac hypertrophy, although the relevance of this paradigm to hypertrophy regulation in vivo has not been examined.
  
  
  RESULTS
  Here we generated heart-specific transgenic mice with a putative caveolae-targeted LTCC activator protein that was ineffective in initiating or enhancing cardiac hypertrophy in vivo. We also generated transgenic mice with cardiac-specific overexpression of a putative caveolae-targeted inhibitor of LTCCs, and while this protein inhibited caveolae-localized LTCCs without effects on global Ca2+ handling, it similarly had no effect on cardiac hypertrophy in vivo. Cardiac hypertrophy was elicited by pressure overload for 2 or 12 weeks or with neurohumoral agonist infusion. Caveolae-specific LTCC activator or inhibitor transgenic mice showed no greater change in nuclear factor of activated T-cells activity after 2 weeks of pressure overload stimulation compared with control mice.
  
  
  CONCLUSIONS
  Our results indicate that LTCCs in the caveolae microdomain do not affect cardiac function and are not necessary for the regulation of hypertrophic signaling in the adult mouse heart.
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 240 Albert Sabin Way, Cincinnati, OH 45229, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Correll
authors.affiliation: Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Makarewich
authors.affiliation: Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 240 Albert Sabin Way, Cincinnati, OH 45229, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Sargent
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 240 Albert Sabin Way, Cincinnati, OH 45229, USA.
authors.forename: Allen J
authors.initials: AJ
authors.lastname: York
authors.affiliation: Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Remus M
authors.initials: RM
authors.lastname: Berretta
authors.affiliation: Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Houser
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 240 Albert Sabin Way, Cincinnati, OH 45229, USA.|Department of Pediatrics, Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229-3039, USA.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Molkentin
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002415:Cats; D021941:Caveolae / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008822:Mice, Transgenic; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D010641:Phenotype; D013997:Time Factors; D014162:Transfection; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016277:Ventricular Function, Left
chemical_list: C491528:Cacnb2 protein, mouse; D020746:Calcium Channels, L-Type; D050778:NFATC Transcription Factors; D020559:Monomeric GTP-Binding Proteins
keywords: Calcium; Cardiac myocytes; Hypertrophy; Signalling