Systems biology of skeletal muscle: Fiber type as an organizing principle
Skeletal muscle force generation and contraction are fundamental to countless aspects of human life. The complexity of skeletal muscle physiology is simplified by fiber type classification where differences are observed from neuromuscular transmission to release of intracellular Ca2+ from the sarcoplasmic reticulum and the resulting recruitment and cycling of cross-bridges. This review uses fiber type classification as an organizing and simplifying principle to explore the complex interactions between the major proteins involved in muscle force generation and contraction. WIREs Syst Biol Med 2012. doi: 10.1002/wsbm.1184
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Available from: Maria Lynn Spletter
- "While further details of upstream regulation are unclear, the expression of MyHC isoforms with different molecular properties, for example variable cross-bridge lengths with actin during contraction, underlies part of the functional differences between fiber types (reviewed in [11,24]). Additionally, specific MyHC isoforms are combined with fiber type-specific isoforms of the Troponin–Tropomyosin complex to adjust the calcium sensitivity of different fiber types. "
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ABSTRACT: Muscles coordinate body movements throughout the animal kingdom. Each skeletal muscle is built of large, multi-nucleated cells, called myofibers, which are classified into several functionally distinct types. The typical fiber-type composition of each muscle arises during development, and in mammals is extensively adjusted in response to postnatal exercise. Understanding how functionally distinct muscle fiber-types arise is important for unraveling the molecular basis of diseases from cardiomyopathies to muscular dystrophies. In this review, we focus on recent advances in Drosophila and mammals in understanding how muscle fiber-type specification is controlled by the regulation of transcription and alternative splicing. We illustrate the cooperation of general myogenic transcription factors with muscle fiber-type specific transcriptional regulators as a basic principle for fiber-type specification, which is conserved from flies to mammals. We also examine how regulated alternative splicing of sarcomeric proteins in both flies and mammals can directly instruct the physiological and biophysical differences between fiber-types. Thus, research in Drosophila can provide important mechanistic insight into muscle fiber specification, which is relevant to homologous processes in mammals and to the pathology of muscle diseases.
Available from: Gary C Sieck
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ABSTRACT: The diaphragm muscle (DIAm) is critically responsible for sustaining ventilation. Previously we showed in a commonly used model of spinal cord injury, unilateral spinal cord hemisection at C(2) (SH), that there are minimal changes to muscle fiber cross-sectional area (CSA) and fiber type distribution following 14 days of SH-induced ipsilateral DIAm inactivity. In the present study effects of long-term SH-induced inactivity on DIAm fiber size and force were examined. We hypothesized that prolonged inactivity would not result in substantial DIAm atrophy or force loss. Adult rats were randomized to control or SH groups (n=34 total). Chronic bilateral DIAm EMG activity was monitored during resting breathing. Minimal levels of spontaneous recovery of ipsilateral DIAm EMG activity were evident in 42% of SH rats (<25% of pre-injury root-mean square amplitude). Following 42 days of SH, DIAm specific force was reduced 39%. There was no difference in CSA for type I or IIa DIAm fibers in SH rats compared to age, weight-matched controls (classification based on myosin heavy chain isoform expression). Type IIx and/or IIb DIAm fibers displayed a modest 20% reduction in CSA (p<0.05). Overall, there were no differences in the distribution of fiber types or the contribution of each fiber type to the total DIAm CSA. These data indicate that reduced specific force following prolonged inactivity of the DIAm is associated with modest, fiber type-selective adaptations in muscle fiber size and fiber type distribution.
Available from: Bert Blaauw
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ABSTRACT: Mammalian skeletal muscles are composed of a variety of highly specialized fibers whose selective recruitment allows muscles to fulfill their diverse functional tasks. In addition, skeletal muscle fibers can change their structural and functional properties to perform new tasks or respond to new conditions. The adaptive changes of muscle fibers can occur in response to variations in the pattern of neural stimulation, loading conditions, availability of substrates, and hormonal signals. The new conditions can be detected by multiple sensors, from membrane receptors for hormones and cytokines, to metabolic sensors, which detect high-energy phosphate concentration, oxygen and oxygen free radicals, to calcium binding proteins, which sense variations in intracellular calcium induced by nerve activity, to load sensors located in the sarcomeric and sarcolemmal cytoskeleton. These sensors trigger cascades of signaling pathways which may ultimately lead to changes in fiber size and fiber type. Changes in fiber size reflect an imbalance in protein turnover with either protein accumulation, leading to muscle hypertrophy, or protein loss, with consequent muscle atrophy. Changes in fiber type reflect a reprogramming of gene transcription leading to a remodeling of fiber contractile properties (slow-fast transitions) or metabolic profile (glycolytic-oxidative transitions). While myonuclei are in postmitotic state, satellite cells represent a reserve of new nuclei and can be involved in the adaptive response. © 2013 American Physiological Society. Compr Physiol 3:1645-1687, 2013.
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