In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 110, No. 5 ( 2012-03-02), p. 669-674
Abstract:
The source of Ca 2+ to activate pathological cardiac hypertrophy is not clearly defined. Ca 2+ influx through the L-type Ca 2+ channels (LTCCs) determines “contractile” Ca 2+ , which is not thought to be the source of “hypertrophic” Ca 2+ . However, some LTCCs are housed in caveolin-3 (Cav-3)–enriched signaling microdomains and are not directly involved in contraction. The function of these LTCCs is unknown. Objective: To test the idea that LTCCs in Cav-3–containing signaling domains are a source of Ca 2+ to activate the calcineurin–nuclear factor of activated T-cell signaling cascade that promotes pathological hypertrophy. Methods and Results: We developed reagents that targeted Ca 2+ channel-blocking Rem proteins to Cav-3–containing membranes, which house a small fraction of cardiac LTCCs. Blocking LTCCs within this Cav-3 membrane domain eliminated a small fraction of the LTCC current and almost all of the Ca 2+ influx-induced NFAT nuclear translocation, but it did not reduce myocyte contractility. Conclusions: We provide proof of concept that Ca 2+ influx through LTCCs within caveolae signaling domains can activate “hypertrophic” signaling, and this Ca 2+ influx can be selectively blocked without reducing cardiac contractility.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/CIRCRESAHA.111.264028
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2012
detail.hit.zdb_id:
1467838-X