Regulation of myofilament force and loaded shortening by skeletal myosin binding protein C
| Autor: | Aikaterini Kontrogianni-Konstantopoulos, Laurin M. Hanft, Kerry S. McDonald, Joel C. Robinett, Janelle Geist |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Sarcomeres 0301 basic medicine Myofilament Contraction (grammar) Physiology Myosins Microfilament Sarcomere Rats Sprague-Dawley Protein filament 03 medical and health sciences 0302 clinical medicine Myofibrils Commentaries Myosin Animals Phosphorylation Protein kinase A Research Articles Actin Chemistry musculoskeletal system Cyclic AMP-Dependent Protein Kinases Rats Actin Cytoskeleton 030104 developmental biology Muscle Fibers Fast-Twitch Commentary Biophysics Calcium Carrier Proteins 030217 neurology & neurosurgery Research Article Protein C Muscle Contraction |
| Zdroj: | The Journal of General Physiology |
| ISSN: | 1540-7748 0022-1295 |
| Popis: | Myosin binding protein C (MyBP-C) is thought to regulate the contraction of skeletal muscle. Robinett et al. show that phosphorylation of slow skeletal MyBP-C modulates contraction by recruiting cross-bridges, modifying cross-bridge kinetics, and altering internal drag forces in the C-zone. Myosin binding protein C (MyBP-C) is a 125–140-kD protein located in the C-zone of each half-thick filament. It is thought to be an important regulator of contraction, but its precise role is unclear. Here we investigate mechanisms by which skeletal MyBP-C regulates myofilament function using rat permeabilized skeletal muscle fibers. We mount either slow-twitch or fast-twitch skeletal muscle fibers between a force transducer and motor, use Ca2+ to activate a range of forces, and measure contractile properties including transient force overshoot, rate of force development, and loaded sarcomere shortening. The transient force overshoot is greater in slow-twitch than fast-twitch fibers at all Ca2+ activation levels. In slow-twitch fibers, protein kinase A (PKA) treatment (a) augments phosphorylation of slow skeletal MyBP-C (sMyBP-C), (b) doubles the magnitude of the relative transient force overshoot at low Ca2+ activation levels, and (c) increases force development rates at all Ca2+ activation levels. We also investigate the role that phosphorylated and dephosphorylated sMyBP-C plays in loaded sarcomere shortening. We test the hypothesis that MyBP-C acts as a brake to filament sliding within the myofilament lattice by measuring sarcomere shortening as thin filaments traverse into the C-zone during lightly loaded slow-twitch fiber contractions. Before PKA treatment, shortening velocity decelerates as sarcomeres traverse from ∼3.10 to ∼3.00 µm. After PKA treatment, sarcomeres shorten a greater distance and exhibit less deceleration during similar force clamps. After sMyBP-C dephosphorylation, sarcomere length traces display a brief recoil (i.e., “bump”) that initiates at ∼3.06 µm during loaded shortening. Interestingly, the timing of the bump shifts with changes in load but manifests at the same sarcomere length. Our results suggest that sMyBP-C and its phosphorylation state regulate sarcomere contraction by a combination of cross-bridge recruitment, modification of cross-bridge cycling kinetics, and alteration of drag forces that originate in the C-zone. |
| Databáze: | OpenAIRE |
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