Skip Navigation

Cardiovascular Research 2006 69(4):816-824; doi:10.1016/j.cardiores.2005.10.006
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Calaghan, S.
Right arrow Articles by White, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Calaghan, S.
Right arrow Articles by White, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2005, European Society of Cardiology

Caveolae modulate excitation–contraction coupling and β2-adrenergic signalling in adult rat ventricular myocytes

Sarah Calaghan* and Ed White

Research Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9NQ, UK

* Corresponding author. Tel.: +44 113 343 4309; fax: +44 113 343 4228. Email address: s.c.calaghan{at}leeds.ac.uk

Objective: Caveolae, flask shaped invaginations of the cell membrane, influence signalling cascades in many cell types. We have tested the hypothesis that caveolae modulate excitation–contraction coupling (ECC) and β-adrenergic stimulation in the adult cardiac myocyte.

Methods: Shortening, [Ca2+]i and L-type Ca2+ current (ICa,L) were recorded in rat ventricular myocytes. Caveolae were disrupted with methyl-β-cyclodextrin (MβC).

Results: Shortening and [Ca2+]i transient amplitude were reduced in myocytes treated with MβC. MβC did not alter the density or characteristics of ICa,L or the sarcoplasmic reticulum (SR) Ca2+ load, but significantly reduced fractional SR Ca2+ release. The inotropic response of myocytes to β1-adrenoceptor stimulation was insensitive to caveolae disruption. By contrast, the increase in shortening, [Ca2+]i transient and ICa,L seen following β2 stimulation was markedly enhanced (3–5 fold) following MβC treatment, and the effect on ICa,L could be mimicked by dialyzing cells with an antibody to caveolin 3. When the G{alpha}i pathway was disabled with pertussis toxin (PTX), control cells showed a similar response to β2 stimulation as seen in MβC-treated myocytes, whereas MβC-treated cells were insensitive to PTX.

Conclusions: Caveolae modulate ECC via the efficiency of the Ca2+-induced Ca2+ release process, rather than Ca2+ influx. Our data are also consistent with the hypothesis that interaction of Gi protein cascade components with caveolin in the caveolae is necessary for effective signalling by this pathway. This suggests that changes in caveolin expression in the adult heart seen during aging and in disease will have consequences for baseline cardiac function and β-adrenergic responsiveness.

KEYWORDS Caveolae; Calcium; Adrenergic agonists; Ca-channel; Signal transduction

Time for primary review 34 days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.