Hypoosmotic shocks induce elevation of resting calcium level in duchenne muscular dystrophy myotubes contracting in vitro

Imbert, Nathalie; Vandebrouck, Clarisse; Constantin, Bruno; Duport, G; Guillou, C.; Cognard, Christian; Raymond, Guy

doi:10.1016/0960-8966(96)00351-3

Cited by 47 publications

(32 citation statements)

References 40 publications

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“…Calcium entry could also be regulated through a multitude of SOCs: α1-syntrophin and PKCα could balance the activity of Stim1/ Orai1/Trpc1 genes (Sabourin et al, 2012;Harisseh et al, 2013). In addition to altered expression of Orai1, we observed an overexpression of Trpc1 and Ryr1, in accordance with previously reported data (Carrasco and Figueroa, 1995;Imbert et al, 1996;Bellinger et al, 2009;Morel et al, 2009;Andersson et al, 2012). Calcium concentration has a well-known importance in the development of DMD pathogenesis.…”

Section: Discussionsupporting

confidence: 80%

“…Deval et al suggested that increased calcium release from the sarcoplasmic reticulum (SR) is involved in calcium dysregulation in DMD myotubes (Deval et al, 2002). The high sensitivity to calcium of dystrophic muscle cells is dependent on two specialized intracellular Ca 2+ -releasing channels located at the SR membrane: the ryanodine receptor 1 (Ryr1) and inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) (Carrasco and Figueroa, 1995;Imbert et al, 1996). Recently, Bellinger et al identified a structural and functional defect in Ryr1 in mdx muscles (Bellinger et al, 2009), and Morel and others suggested that Ryr1 expression could be altered also in vascular myocytes of mdx mice (Morel et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling mediates delayed myogenesis in Duchenne muscular dystrophy fetal muscle

Farini¹,

Sitzia²,

Cassinelli³

et al. 2016

Journal of Cell Science

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Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder characterized by muscle wasting and premature death. The defective gene is dystrophin, a structural protein, absence of which causes membrane fragility and myofiber necrosis. Several lines of evidence showed that in adult DMD patients dystrophin is involved in signaling pathways that regulate calcium homeostasis and differentiation programs. However, secondary aspects of the disease, such as inflammation and fibrosis development, might represent a bias in the analysis. Because fetal muscle is not influenced by gravity and does not suffer from mechanical load and/or inflammation, we investigated 12-week-old fetal DMD skeletal muscles, highlighting for the first time early alterations in signaling pathways mediated by the absence of dystrophin itself. We found that PLC/IP3/IP3R/Ryr1/Ca 2+ signaling is widely active in fetal DMD skeletal muscles and, through the calcium-dependent PKCα protein, exerts a fundamental regulatory role in delaying myogenesis and in myofiber commitment. These data provide new insights into the origin of DMD pathology during muscle development.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling mediates delayed myogenesis in Duchenne muscular dystrophy fetal muscle

Farini¹,

Sitzia²,

Cassinelli³

et al. 2016

Journal of Cell Science

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“…Moreover, stretch-activated currents share similar electrophysiological properties with store-operated currents when recorded at the surface membrane of skeletal fibers (23). Stretch-activated currents (27,60) and osmotic activated calcium entry (33) are increased in mdx and DMD muscle cells lacking dystrophin and DAPC. It is thus possible that the loss of the PDZ-mediated regulation by ␣1-syntrophin in dystrophin-deficient muscles enhances the mechanical sensitivity of TRPC1-containing channels.…”

Section: Discussionmentioning

confidence: 95%

Regulation of TRPC1 and TRPC4 Cation Channels Requires an α1-Syntrophin-dependent Complex in Skeletal Mouse Myotubes

Sabourin

Lamiche

Vandebrouck

et al. 2009

Journal of Biological Chemistry

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The dystrophin-associated protein complex (DAPC) is essential for skeletal muscle, and the lack of dystrophin in Duchenne muscular dystrophy results in a reduction of DAPC components such as syntrophins and in fiber necrosis. By anchoring various molecules, the syntrophins may confer a role in cell signaling to the DAPC. Calcium disorders and abnormally elevated cation influx in dystrophic muscle cells have suggested that the DAPC regulates some sarcolemmal cationic channels. We demonstrated previously that minidystrophin and ␣1-syntrophin restore normal cation entry in dystrophin-deficient myotubes and that sarcolemmal TRPC1 channels associate with dystrophin and the bound PDZ domain of ␣1-syntrophin. This study shows that small interfering RNA (siRNA) silencing of ␣1-syntrophin dysregulated cation influx in myotubes. Moreover, deletion of the PDZcontaining domain prevented restoration of normal cation entry by ␣1-syntrophin transfection in dystrophin-deficient myotubes. TRPC1 and TRPC4 channels are expressed at the sarcolemma of muscle cells; forced expression or siRNA silencing showed that cation influx regulated by ␣1-syntrophin is supported by TRPC1 and TRPC4. A molecular association was found between TRPC1 and TRPC4 channels and the ␣1-syntrophin-dystrophin complex. TRPC1 and TRPC4 channels may form sarcolemmal channels anchored to the DAPC, and ␣1-syntrophin is necessary to maintain the normal regulation of TRPC-supported cation entry in skeletal muscle. Cation channels with DAPC form a signaling complex that modulates cation entry and may be crucial for normal calcium homeostasis in skeletal muscles.

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“…The main goals of this study were to determine whether differences in calcium movement properties can be observed between normal and DMD skeletal muscle cells co-cultured (contracting) with neuronal explants and whether these differences can in some way be involved in resting intracellular calcium concentration disorders observed in co-cultured DMD cells (Imbert et al 1995(Imbert et al , 1996. The present study provides three kinds of data.…”

Section: Discussionmentioning

confidence: 97%

“…This view is reinforced by the observation that both types of calcium current were altered. Experiments by Imbert et al (1996) and Vandebrouck et al (2001) suggest that other channels and their regulation/expression could be altered in cocultured DMD muscle cells, in particular cationic channels displaying mechano-sensitive properties. Finally, our present overall hypothesis is that DMD muscle membranes display a general deregulation effect on channel proteins, with a variable level of consequences depending on the particular transmembrane protein affected.…”

Section: Ultrastructurementioning

confidence: 99%

Calcium currents and transients in co‐cultured contracting normal and Duchenne muscular dystrophy human myotubes

Imbert

Vandebrouck

Duport

et al. 2001

The Journal of Physiology

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1. The goal of the present study was to investigate differences in calcium movements between normal and Duchenne muscular dystrophy (DMD) human contracting myotubes co-cultured with explants of rat spinal cord with attached dorsal root ganglia. Membrane potential, variations of intracellular calcium concentration and T-and L-type calcium currents were recorded. Further, a descriptive and quantitative study by electron microscopy of the ultrastructure of the co-cultures was carried out.2. The resting membrane potential was slightly less negative in DMD (_61.4 ± 1.1 mV) than in normal myotubes (_65.5 ± 0.9 mV). Both types of myotube displayed spontaneous action potentials (mean firing frequency, 0.42 and 0.16 Hz, respectively), which triggered spontaneous calcium transients measured with Indo-1.3. The time integral under the spontaneous Ca 2+ transients was significantly greater in DMD myotubes (97 ± 8 nM s) than in normal myotubes (67 ± 13 nM s).4. The L-and T-type current densities estimated from patch-clamp recordings were smaller in DMD cells (2.0 ± 0.5 and 0.90 ± 0.19 pA pF _1 , respectively) than in normal cells (3.9 ± 0.7 and 1.39 ± 0.30 pA pF _1 , respectively). The voltage-dependent inactivation relationships revealed a shift in the conditioning potentialat which inactivation is half-maximal (V h,0.5 ) of the T-and L-type currents towards less negative potentials, from _72.1 ± 0.7 and _53.7 ± 1.5 mV in normal cells to _61.9 ± 1.4 and _29.2 ± 1.4 mV in DMD cells, respectively.6. Both descriptive and quantitative studies by electron microscopy suggested a more advanced development of DMD myotubes as compared to normal ones. This conclusion was supported by the significantly larger capacitance of the DMD myotubes (408 ± 45 pF) than of the normal myotubes (299 ± 34 pF) of the same apparent size.7. Taken together, these results show that differences in T-and L-type calcium currents between normal and DMD myotubes cannot simply explain all observed alterations in calcium homeostasis in DMD myotubes, thus suggesting that other transmembrane calcium transport mechanisms must also be altered in DMD myotubes compared with normal myotubes.

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Hypoosmotic shocks induce elevation of resting calcium level in duchenne muscular dystrophy myotubes contracting in vitro

Cited by 47 publications

References 40 publications

Inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling mediates delayed myogenesis in Duchenne muscular dystrophy fetal muscle

Inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling mediates delayed myogenesis in Duchenne muscular dystrophy fetal muscle

Regulation of TRPC1 and TRPC4 Cation Channels Requires an α1-Syntrophin-dependent Complex in Skeletal Mouse Myotubes

Calcium currents and transients in co‐cultured contracting normal and Duchenne muscular dystrophy human myotubes

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