Reference : Impaired neuromuscular transmission and skeletal muscle fiber necrosis in mice lackin...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Life sciences : Biochemistry, biophysics & molecular biology
Impaired neuromuscular transmission and skeletal muscle fiber necrosis in mice lacking Na/Ca exchanger 3
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 mailto [Université de Liège - ULiège > Département de sciences fonctionnelles > Biochimie métabolique vétérinaire >]
Journal of Clinical Investigation
American Society for Clinical Investigation
Yes (verified by ORBi)
Ann Arbor
[en] neuromuscular transmission ; skeletal muscle fiber ; necrosis ; mice ; Na/Ca exchanger 3
[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
S. Sokolow was supported by FNRS, the Belgian Telethon, and the Fondation Rose. This work was supported by the Belgian Telethon, a grant from the Université Libre de Bruxelles, by the Fonds de la Recherche Scientifique Médicale de Belgique (to S. Schurmans), by the Association française contre les myopathies (AFM) (to P. Gailly and J. Molgó), by an Action de Recherche Concertée grant (00/05-260) from the General Direction of Scientific Research of the French Community of Belgium (to P. Gailly) and by the Fondation Médicale Reine Elisabeth and the Fondation Universitaire David and Alice Van Buuren (to J.-M. Vanderwinden)
Researchers ; Professionals
Nonstandard abbreviations used: electromyography (EMG); cytosolic free calcium concentration ([Ca2+]i); Na/Ca exchanger (NCX); neuromuscular junction (NMJ); vesicular acetylcholine transporter (VAChT); plasma membrane Ca2+ ATPase type 1 (PMCA1); flexor digitorum brevis (FDB); N-methyl-D-glucamine (NMDG); Evans blue dye (EBD); compound muscle action potential (CMAP); hypoxanthine phosphoribosyltransferase (HPRT); single-fiber electromyography (SFEMG); single-fiber action potential (SFAP); mean consecutive discharge (MCD); evoked endplate potential (EPP); spontaneous miniature endplate potential (MEPP); embryonic stem (ES); NCX3 immunoreactivity (NCX3-ir); sarcoplasmic reticulum (SR); 2,5-di(tert-butyl)-1,4-benzohydroquinone (TBQ); SR Ca2+ ATPase (SERCA); repetitive nerve stimulation (RNS); low rate of repetitive stimulation (LRRS); high rate of repetitive stimulation (HRRS)

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