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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chin, Eva R. Chen, Dapeng Bobyk, Kostyantyn D. Mázala, Davi A. G. |
| Description | Author Affiliation: Chin ER ( School of Public Health, University of Maryland, College Park, Maryland erchin@umd.edu.); Chen D ( School of Public Health, University of Maryland, College Park, Maryland.); Bobyk KD ( School of Public Health, University of Maryland, College Park, Maryland.); Mázala DA ( School of Public Health, University of Maryland, College Park, Maryland.) |
| Abstract | Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by skeletal muscle atrophy and weakness, ultimately leading to respiratory failure. The purpose of this study was to assess changes in skeletal muscle excitation-contraction (E-C) coupling and intracellular Ca(2+) handling during disease progression in the G93A*SOD1 ALS transgenic (ALS Tg) mouse model. To assess E-C coupling, single muscle fibers were electrically stimulated (10-150 Hz), and intracellular free Ca(2+) concentration was assessed using fura-2. There were no differences in peak fura-2 ratio at any stimulation frequency at 70 days (early presymptomatic). However, at 90 days (late presymptomatic) and 120-140 days (symptomatic), fura-2 ratio was increased at 10 Hz in ALS Tg compared with wild-type (WT) fibers (0.670 ± 0.02 vs. 0.585 ± 0.02 for 120-140 days; P < 0.05). There was also a significant increase in resting fura-2 ratio at 90 days (0.351 ± 0.008 vs. 0.390 ± 0.009 in WT vs. ALS Tg; P < 0.05) and 120-140 days (0.374 ± 0.001 vs. 0.415 ± 0.003 in WT vs. ALS Tg; P < 0.05). These increases in intracellular Ca(2+) in ALS Tg muscle were associated with reductions in the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase proteins SERCA1 (to 54% and 19% of WT) and SERCA2 (to 56% and 11% of WT) and parvalbumin (to 80 and 62% of WT) in gastrocnemius muscle at 90 and 120-140 days, respectively. There was no change in dihydropyridine receptor/l-type Ca(2+) channel at any age. Overall, these data demonstrate minimal changes in electrically evoked Ca(2+) transients but elevations in intracellular Ca(2+) attributable to decreased Ca(2+)-clearance proteins. These data suggest that elevations in cellular Ca(2+) could contribute to muscle weakness during disease progression in ALS mice. |
| File Format | HTM / HTML |
| ISSN | 03636143 |
| e-ISSN | 15221563 |
| DOI | 10.1152/ajpcell.00237.2013 |
| Journal | American Journal of Physiology - Cell Physiology |
| Issue Number | 11 |
| Volume Number | 307 |
| Language | English |
| Publisher | American Physiological Society |
| Publisher Date | 2014-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Cell Biology Amyotrophic Lateral Sclerosis Metabolism Calcium Muscle, Skeletal Superoxide Dismutase Aging Animals Gene Expression Regulation, Enzymologic Mice Mice, Transgenic Muscle Strength Genetics Physiology Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Physiology |
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