scholarly journals Biophysical Properties of a Novel Cationic Channel in the Outer and Inner Membranes of Nuclei from Adult Skeletal Muscle Fibers

2012 ◽  
Vol 102 (3) ◽  
pp. 104a-105a
Author(s):  
Viktor Yarotskyy ◽  
Robert T. Dirksen
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fibers ◽  
Biophysical Properties ◽  
Adult Skeletal Muscle ◽  
Skeletal Muscle Fibers ◽  
Cationic Channel

scholarly journals Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers

2001 ◽  
Vol 155 (1) ◽  
pp. 27-40 ◽  
Author(s):  
Yewei Liu ◽  
Zoltán Cseresnyés ◽  
William R. Randall ◽  
Martin F. Schneider
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Nuclear Translocation ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Adult Skeletal Muscle ◽  
Skeletal Muscle Fibers ◽  
Slow Twitch ◽  
Nuclear Foci ◽  
Fast Twitch

TTranscription factor nuclear factor of activated T cells NFATc (NFATc1, NFAT2) may contribute to slow-twitch skeletal muscle fiber type–specific gene expression. Green fluorescence protein (GFP) or FLAG fusion proteins of either wild-type or constitutively active mutant NFATc [NFATc(S→A)] were expressed in cultured adult mouse skeletal muscle fibers from flexor digitorum brevis (predominantly fast-twitch). Unstimulated fibers expressing NFATc(S→A) exhibited a distinct intranuclear pattern of NFATc foci. In unstimulated fibers expressing NFATc–GFP, fluorescence was localized at the sarcomeric z-lines and absent from nuclei. Electrical stimulation using activity patterns typical of slow-twitch muscle, either continuously at 10 Hz or in 5-s trains at 10 Hz every 50 s, caused cyclosporin A–sensitive appearance of fluorescent foci of NFATc–GFP in all nuclei. Fluorescence of nuclear foci increased during the first hour of stimulation and then remained constant during a second hour of stimulation. Kinase inhibitors and ionomycin caused appearance of nuclear foci of NFATc–GFP without electrical stimulation. Nuclear translocation of NFATc–GFP did not occur with either continuous 1 Hz stimulation or with the fast-twitch fiber activity pattern of 0.1-s trains at 50 Hz every 50 s. The stimulation pattern–dependent nuclear translocation of NFATc demonstrated here could thus contribute to fast-twitch to slow-twitch fiber type transformation.

scholarly journals Activity- and Calcineurin-independent Nuclear Shuttling of NFATc1, but Not NFATc3, in Adult Skeletal Muscle Fibers

2006 ◽  
Vol 17 (4) ◽  
pp. 1570-1582 ◽  
Author(s):  
Tiansheng Shen ◽  
Yewei Liu ◽  
Zoltán Cseresnyés ◽  
Arie Hawkins ◽  
William R. Randall ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Nuclear Export ◽  
Muscle Fibers ◽  
Nuclear Accumulation ◽  
Leptomycin B ◽  
Adult Skeletal Muscle ◽  
Casein Kinase 1 ◽  
Nuclear Uptake ◽  
Skeletal Muscle Fibers

The transcription factor NFATc1 may be involved in slow skeletal muscle gene expression. NFATc1 translocates from cytoplasm to nuclei during slow fiber type electrical stimulation of skeletal muscle fibers because of activation of the Ca2+-dependent phosphatase calcineurin, resulting in nuclear factor of activated T-cells (NFAT) dephosphorylation and consequent exposure of its nuclear localization signal. Here, we find that unstimulated adult skeletal muscle fibers exhibit a previously unanticipated nucleocytoplasmic shuttling of NFATc1 without appreciable nuclear accumulation. In resting fibers, the nuclear export inhibitor leptomycin B caused nuclear accumulation of NFATc1 (but not of isoform NFATc3) and formation of NFATc1 intranuclear bodies independent of calcineurin. The rate of nuclear uptake of NFATc1 was 4.6 times lower in resting fibers exposed to leptomycin B than during electrical stimulation. Inhibitors of glycogen synthase kinase and protein kinase A or of casein kinase 1 slowed the decay of nuclear NFATc1 after electrical stimulation, but they did not cause NFATc1 nuclear uptake in unstimulated fibers. We propose that two nuclear translocation pathways, one pathway mediated by calcineurin activation and NFAT dephosphorylation and the other pathway independent of calcineurin and possibly independent of NFAT dephosphorylation, determine the distribution of NFATc1 between cytoplasm and nuclei in adult skeletal muscle.

scholarly journals Effect of agrin on the distribution of acetylcholine receptors and sodium channels on adult skeletal muscle fibers in culture.

1991 ◽  
Vol 115 (3) ◽  
pp. 765-778 ◽  
Author(s):  
M T Lupa ◽  
J H Caldwell
Keyword(s):  
Skeletal Muscle ◽  
Acetylcholine Receptors ◽  
Muscle Fibers ◽  
Postsynaptic Membrane ◽  
Na Channel ◽  
High Concentration ◽  
Achr Cluster ◽  
Adult Skeletal Muscle ◽  
Skeletal Muscle Fibers ◽  
Alpha Bungarotoxin

We used the loose patch voltage clamp technique and rhodamine-conjugated alpha-bungarotoxin to study the regulation of Na channel (NaCh) and acetylcholine receptor (AChR) distribution on dissociated adult skeletal muscle fibers in culture. The aggregate of AChRs and NaChs normally found in the postsynaptic membrane of these cells gradually fragmented and dispersed from the synaptic region after several days in culture. This dispersal was the result of the collagenase treatment used to dissociate the cells, suggesting that a factor associated with the extracellular matrix was responsible for maintaining the high concentration of AchRs and NaChs at the neuromuscular junction. We tested whether the basal lamina protein agrin, which has been shown to induce the aggregation of AChRs on embryonic myotubes, could similarly influence the distribution of NaChs. By following identified fibers, we found that agrin accelerated both the fragmentation of the endplate AChR cluster into smaller patches as well as the appearance of new AChR clusters away from the endplate. AChR patches which were fragments of the original endplate retained a high density of NaChs, but no new NaCh hotspots were found elsewhere on the fiber, including sites of newly formed AChR clusters. The results are consistent with the hypothesis that extracellular signals regulate the distribution of AChRs and NaChs on skeletal muscle fibers. While agrin probably serves this function for the AChR, it does not appear to play a role in the regulation of the NaCh distribution.

scholarly journals Foxo1 nucleo-cytoplasmic distribution and unidirectional nuclear influx are the same in nuclei in a single skeletal muscle fiber but vary between fibers

2018 ◽  
Vol 314 (3) ◽  
pp. C334-C348 ◽  
Author(s):  
Yewei Liu ◽  
Sarah J. Russell ◽  
Martin F. Schneider
Keyword(s):  
Skeletal Muscle ◽  
Fluorescent Protein ◽  
Muscle Fibers ◽  
Culture Conditions ◽  
Control Culture ◽  
Adult Skeletal Muscle ◽  
Large Variability ◽  
Skeletal Muscle Fibers ◽  
Foxo Transcription Factors ◽  
Green Fluorescent

Foxo transcription factors promote protein breakdown and atrophy of skeletal muscle fibers. Foxo transcriptional effectiveness is largely determined by phosphorylation-dependent nucleo-cytoplasmic shuttling. Imaging Foxo1-green fluorescent protein (GFP) over time in 124 nuclei in 68 multinucleated adult skeletal muscle fibers under control culture conditions reveals large variability between fibers in Foxo1-GFP nucleo-cytoplasmic concentration ratio (N/C) and in the apparent rate coefficient ( kI′) for Foxo1-GFP unidirectional nuclear influx (measured with efflux blocked by leptomycin B). Pairs of values of N/C or of kI′ from different nuclei in the same fiber were essentially the same, but only weakly correlated in nuclei from different fibers in the same culture well. Thus, fiber to fiber variability of cellular factors, but not extracellular factors, determines Foxo1 distribution. Over all nuclei, N/C and kI′ were closely proportional, indicating that kI′ is the major determinant of Foxo1 distribution. IGF-I activation of Foxo kinase Akt reduces variability by decreasing kI′ and N/C in all fibers. However, inhibiting Akt did not drive kI′ uniformly high, indicating other pathways in Foxo1 regulation.

scholarly journals Involvement of TRPC in the abnormal calcium influx observed in dystrophic (mdx) mouse skeletal muscle fibers

2002 ◽  
Vol 158 (6) ◽  
pp. 1089-1096 ◽  
Author(s):  
Clarisse Vandebrouck ◽  
Dominique Martin ◽  
Monique Colson-Van Schoor ◽  
Huguette Debaix ◽  
Philippe Gailly
Keyword(s):  
Skeletal Muscle ◽  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Surface Membrane ◽  
Muscle Fibers ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Patch Clamp Technique ◽  
Adult Skeletal Muscle ◽  
Skeletal Muscle Fibers

Duchenne muscular dystrophy results from the lack of dystrophin, a cytoskeletal protein associated with the inner surface membrane, in skeletal muscle. The absence of dystrophin induces an abnormal increase of sarcolemmal calcium influx through cationic channels in adult skeletal muscle fibers from dystrophic (mdx) mice. We observed that the activity of these channels was increased after depletion of the stores of calcium with thapsigargin or caffeine. By analogy with the situation observed in nonexcitable cells, we therefore hypothesized that these store-operated channels could belong to the transient receptor potential channel (TRPC) family. We measured the expression of TRPC isoforms in normal and mdx adult skeletal muscles fibers, and among the seven known isoforms, five were detected (TRPC1, 2, 3, 4, and 6) by RT-PCR. Western blot analysis and immunocytochemistry of normal and mdx muscle fibers demonstrated the localization of TRPC1, 4, and 6 proteins at the plasma membrane. Therefore, an antisense strategy was used to repress these TRPC isoforms. In parallel with the repression of the TRPCs, we observed that the occurrence of calcium leak channels was decreased to one tenth of its control value (patch-clamp technique), showing the involvement of TRPC in the abnormal calcium influx observed in dystrophic fibers.

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