edoc

Alterations of excitation-contraction coupling and excitation coupled Ca(2+) entry in human myotubes carrying CAV3 mutations linked to rippling muscle

Ullrich, N. D. and Fischer, D. and Kornblum, C. and Walter, M. C. and Niggli, E. and Zorzato, F. and Treves, S.. (2011) Alterations of excitation-contraction coupling and excitation coupled Ca(2+) entry in human myotubes carrying CAV3 mutations linked to rippling muscle. Human Mutation, 32 (3). pp. 309-317.

[img]
Preview
PDF - Accepted Version
3130Kb

Official URL: http://edoc.unibas.ch/dok/A6006957

Downloads: Statistics Overview

Abstract

Rippling muscle disease is caused by mutations in the gene encoding caveolin-3 (CAV3), the muscle-specific isoform of the scaffolding protein caveolin, a protein involved in the formation of caveolae. In healthy muscle, caveolin-3 is responsible for the formation of caveolae, which are highly organized sarcolemmal clusters influencing early muscle differentiation, signalling and Ca(2+) homeostasis. In the present study we examined Ca(2+) homeostasis and excitation-contraction (E-C) coupling in cultured myotubes derived from two patients with Rippling muscle disease with severe reduction in caveolin-3 expression; one patient harboured the heterozygous c.84C<A mutation while the other patient harbored a homozygous splice-site mutation (c.102+ 2T<C) affecting the splice donor site of intron 1 of the CAV3 gene. Our results show that cells from control and rippling muscle disease patients had similar resting [Ca(2+) ](i) and 4-chloro-m-cresol-induced Ca(2+) release but reduced KCl-induced Ca(2+) influx. Detailed analysis of the voltage-dependence of Ca(2+) transients revealed a significant shift of Ca(2+) release activation to higher depolarization levels in CAV3 mutated cells. High resolution immunofluorescence analysis by Total Internal Fluorescence microscopy supports the hypothesis that loss of caveolin-3 leads to microscopic disarrays in the colocalization of the voltage-sensing dihydropyridine receptor and the ryanodine receptor, thereby reducing the efficiency of excitation-contraction coupling.
Faculties and Departments:03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Neuro- und Entwicklungspädiatrie (Weber)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Neuro- und Entwicklungspädiatrie (Weber)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Perioperative Patient Safety (Girard/Treves)
UniBasel Contributors:Fischer, Dirk and Treves, Susan
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:1059-7794
e-ISSN:1098-1004
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:31 May 2017 09:57
Deposited On:27 Mar 2014 13:13

Repository Staff Only: item control page