Involvement of inositol 1,4,5-trisphosphate in nicotinic calcium responses in dystrophic myotubes assessed by near-plasma membrane calcium measurement

In skeletal muscle cells, plasma membrane depolarization causes a rapid calcium release from the sarcoplasmic reticulum through ryanodine receptors triggering contraction. In Duchenne muscular dystrophy (DMD), a lethal disease that is caused by the lack of the cytoskeletal protein dystrophin, the cy...

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Vydáno v:The Journal of biological chemistry Ročník 279; číslo 45; s. 47092
Hlavní autoři: Basset, Olivier, Boittin, François-Xavier, Dorchies, Olivier M, Chatton, Jean-Yves, van Breemen, Cornelis, Ruegg, Urs T
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 05.11.2004
Témata:
Aequorin - chemistry
Animals
Calcium - chemistry
Calcium - metabolism
Calcium Channels - metabolism
Carbachol - pharmacology
Cell Membrane - metabolism
Cholinergic Agonists - pharmacology
Cytosol - metabolism
Egtazic Acid - analogs & derivatives
Egtazic Acid - pharmacology
Green Fluorescent Proteins - metabolism
Inositol 1,4,5-Trisphosphate - physiology
Inositol 1,4,5-Trisphosphate Receptors
Membrane Proteins - metabolism
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Muscle, Skeletal - metabolism
Myocardium - metabolism
Necrosis
Nerve Tissue Proteins - metabolism
Phosphoproteins - chemistry
Plasmids - metabolism
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Nicotinic - metabolism
Sarcoplasmic Reticulum - metabolism
Synaptosomal-Associated Protein 25
Time Factors
Transfection
ISSN:0021-9258
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Shrnutí:In skeletal muscle cells, plasma membrane depolarization causes a rapid calcium release from the sarcoplasmic reticulum through ryanodine receptors triggering contraction. In Duchenne muscular dystrophy (DMD), a lethal disease that is caused by the lack of the cytoskeletal protein dystrophin, the cytosolic calcium concentration is known to be increased, and this increase may lead to cell necrosis. Here, we used myotubes derived from control and mdx mice, the murine model of DMD, to study the calcium responses induced by nicotinic acetylcholine receptor stimulation. The photoprotein aequorin was expressed in the cytosol or targeted to the plasma membrane as a fusion protein with the synaptosome-associated protein SNAP-25, thus allowing calcium measurements in a restricted area localized just below the plasma membrane. The carbachol-induced calcium responses were 4.5 times bigger in dystrophic myotubes than in control myotubes. Moreover, in dystrophic myotubes the carbachol-mediated calcium responses measured in the subsarcolemmal area were at least 10 times bigger than in the bulk cytosol. The initial calcium responses were due to calcium influx into the cells followed by a fast refilling/release phase from the sarcoplasmic reticulum. In addition and unexpectedly, the inositol 1,4,5-trisphosphate receptor pathway was involved in these calcium signals only in the dystrophic myotubes. This surprising involvement of this calcium release channel in the excitation-contraction coupling could open new ways for understanding exercise-induced calcium increases and downstream muscle degeneration in mdx mice and, therefore, in DMD.
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ISSN:0021-9258
DOI:10.1074/jbc.m405054200