[en] We produced and analyzed mice deficient for Na/Ca exchanger 3 (NCX3), a protein that mediates cellular Ca(2+) efflux (forward mode) or Ca(2+) influx (reverse mode) and thus controls intracellular Ca(2+) concentration. NCX3-deficient mice (Ncx3(-/-)) present a skeletal muscle fiber necrosis and a defective neuromuscular transmission, reflecting the absence of NCX3 in the sarcolemma of the muscle fibers and at the neuromuscular junction. The defective neuromuscular transmission is characterized by the presence of electromyographic abnormalities, including low compound muscle action potential amplitude, a decremental response at low-frequency nerve stimulation, an incremental response, and a prominent postexercise facilitation at high-frequency nerve stimulation, as well as neuromuscular blocks. The analysis of quantal transmitter release in Ncx3(-/-) neuromuscular junctions revealed an important facilitation superimposed on the depression of synaptic responses and an elevated delayed release during high-frequency nerve stimulation. It is suggested that Ca(2+) entering nerve terminals is cleared relatively slowly in the absence of NCX3, thereby enhancing residual Ca(2+) and evoked and delayed quantal transmitter release during repetitive nerve stimulation. Our findings indicate that NCX3 plays an important role in vivo in the control of Ca(2+) concentrations in the skeletal muscle fibers and at the neuromuscular junction
Sokolow, S.; Université Libre de Bruxelles - ULB > IRIBHM-IBMM
Manto, M.; Université Libre de Bruxelles - ULB > Laboratory of Experimental Neurology
Gailly, P.; Université Catholique de Louvain - UCL > Department of Physiology
Molgó, J.; Centre National de la Recherche Scientifique, Gif-sur-Yvette, France > Institut Fédératif de Neurobiologie Alfred Fessard, Laboratoire de Neurobiologie Cellulaire et Moléculaire, Unité Propre de Recherche 9040
Vandebrouck, C.; Université Catholique de Louvain - UCL > Department of Physiology
Vanderwinden, J. M.; Université Libre de Bruxelles - ULB > Laboratory of Neurophysiology
Herchuelz, A.; Université Libre de Bruxelles - ULB > Laboratory of Pharmacology and Therapeutics
Schurmans, Stéphane ; Université de Liège - ULiège > Département de sciences fonctionnelles > Biochimie métabolique vétérinaire
Language :
English
Title :
Impaired neuromuscular transmission and skeletal muscle fiber necrosis in mice lacking Na/Ca exchanger 3
Publication date :
2004
Journal title :
Journal of Clinical Investigation
ISSN :
0021-9738
eISSN :
1558-8238
Publisher :
American Society for Clinical Investigation, Ann Arbor, United States - Michigan
Volume :
113
Pages :
265-273
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Belgian Telethon Action de Recherche Concertée grant (00/05-260)
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique ULB - Université Libre de Bruxelles FRSM - Fonds de la Recherche Scientifique Médicale AFM - Association Française contre les Myopathies FMRE - Fondation Médicale Reine Elisabeth
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