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Enhanced dihydropyridine receptor calcium channel activity restores muscle strength in JP45/CASQ1 double knockout mice

Mosca, Barbara and Delbono, Osvaldo and Laura Messi, Maria and Bergamelli, Leda and Wang, Zhong-Min and Vukcevic, Mirko and Lopez, Ruben and Treves, Susan and Nishi, Miyuki and Takeshima, Hiroshi and Paolini, Cecilia and Martini, Marta and Rispoli, Giorgio and Protasi, Feliciano and Zorzato, Francesco. (2013) Enhanced dihydropyridine receptor calcium channel activity restores muscle strength in JP45/CASQ1 double knockout mice. Nature Communications, 4. p. 1541.

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Abstract

Muscle strength declines with age in part due to a decline of Ca(2+) release from sarcoplasmic reticulum calcium stores. Skeletal muscle dihydropyridine receptors (Ca(v)1.1) initiate muscle contraction by activating ryanodine receptors in the sarcoplasmic reticulum. Ca(v)1.1 channel activity is enhanced by a retrograde stimulatory signal delivered by the ryanodine receptor. JP45 is a membrane protein interacting with Ca(v)1.1 and the sarcoplasmic reticulum Ca(2+) storage protein calsequestrin (CASQ1). Here we show that JP45 and CASQ1 strengthen skeletal muscle contraction by modulating Ca(v)1.1 channel activity. Using muscle fibres from JP45 and CASQ1 double knockout mice, we demonstrate that Ca(2+) transients evoked by tetanic stimulation are the result of massive Ca(2+) influx due to enhanced Ca(v)1.1 channel activity, which restores muscle strength in JP45/CASQ1 double knockout mice. We envision that JP45 and CASQ1 may be candidate targets for the development of new therapeutic strategies against decay of skeletal muscle strength caused by a decrease in sarcoplasmic reticulum Ca(2+) content.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Perioperative Patient Safety (Girard/Treves)
UniBasel Contributors:Treves, Susan and Zorzato, Francesco
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:04 May 2017 06:46
Deposited On:06 Mar 2015 07:44

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