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Cited by 393

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

Localization of cardiac L-type Ca 2+ channels to a caveolar macromolecular signaling complex is required for β 2 -adrenergic regulation

Balijepalli, Ravi C., Foell, Jason D., Hall, Duane D., Hell, Johannes W., Kamp, Timothy J.·2006·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0503465103
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Abstract

L-type Ca 2+ channels play a critical role in regulating Ca 2+ -dependent signaling in cardiac myocytes, including excitation-contraction coupling; however, the subcellular localization of cardiac L-type Ca 2+ channels and their regulation are incompletely understood. Caveolae are specialized microdomains of the plasmalemma rich in signaling molecules and supported by the structural protein caveolin-3 in muscle. Here we demonstrate that a subpopulation of L-type Ca 2+ channels is localized to caveolae in ventricular myocytes as part of a macromolecular signaling complex necessary for β 2 -adrenergic receptor (AR) regulation of I Ca,L . Immunofluorescence studies of isolated ventricular myocytes using confocal microscopy detected extensive colocalization of caveolin-3 and the major pore-forming subunit of the L-type Ca channel (Ca v 1.2). Immunogold electron microscopy revealed that these proteins colocalize in caveolae. Immunoprecipitation from ventricular myocytes using anti-Ca v 1.2 or anti-caveolin-3 followed by Western blot analysis showed that caveolin-3, Ca v 1.2, β 2 -AR (not β 1 -AR), G protein α s , adenylyl cyclase, protein kinase A, and protein phosphatase 2a are closely associated. To determine the functional impact of the caveolar-localized β 2 -AR/Ca v 1.2 signaling complex, β 2 -AR stimulation (salbutamol plus atenolol) of I Ca,L was examined in pertussis toxin-treated neonatal mouse ventricular myocytes. The stimulation of I Ca,L in response to β 2 -AR activation was eliminated by disruption of caveolae with 10 mM methyl β-cyclodextrin or by small interfering RNA directed against caveolin-3, whereas β 1 -AR stimulation (norepinephrine plus prazosin) of I Ca,L was not altered. These findings demonstrate that subcellular localization of L-type Ca 2+ channels to caveolar macromolecular signaling complexes is essential for regulation of the channels by specific signaling pathways.

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Metadata

Authors
Balijepalli, R. C., Foell, J. D., Hall, D. D., Hell, J. W., & Kamp, T. J.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2006-05-09
Volume
103
Issue
19
Pages
7500-7505
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0503465103
OpenAlex
W2048777704
Cited by
393
References
34
FWCI
10.49
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Localization of cardiac L-type Ca 2+ channels to a caveolar macromolecular signaling complex is required for β 2 -adrenergic regulation. https://app.cochat.ai/papers/10.1073/pnas.0503465103
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Balijepalli, R. C., Foell, J. D., Hall, D. D., Hell, J. W., & Kamp, T. J. (2006). Localization of cardiac L-type Ca 2+ channels to a caveolar macromolecular signaling complex is required for β 2 -adrenergic regulation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0503465103

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