Myosin Isoforms, Muscle Fiber Types, and Transitions
Abstract
Skeletal muscle is a highly heterogeneous tissue with various fast and slow fiber types. Muscle fibers can adjust their phenotypic properties in response to functional demands. The differences between muscle fiber types are mainly related to their myosin isoforms, specifically myosin heavy chain (MHC) isoforms, which serve as markers for fiber type delineation. This article discusses pure and hybrid fiber types, the conditions that induce transitions between fiber types, and the role of neuromuscular activity, mechanical loading, and hormonal factors in these transitions.
Introduction
Skeletal muscle fiber architecture is unique and contributes to its diverse functional capabilities. Muscle fibers can be classified based on structural and functional properties, with MHC isoforms being the most informative markers. Methods like mATPase histochemistry, immunohistochemistry, and electrophoretic analysis of MHC isoforms have enhanced our understanding of muscle fiber diversity.
Importance of Myosin-Based Fiber Type Classification
Myosin isoforms are crucial for the functional diversity of muscle fibers. Methods assessing myosin differences, such as single fiber electrophoresis, provide detailed information about MHC isoform profiles, which is essential for understanding muscle fiber heterogeneity and functional specialization.
Multiplicity of Myosin Isoforms
Myosin is a hexameric protein composed of heavy and light chains, with 11 MHC isoforms identified in adult extrafusal fibers. These isoforms are expressed in a muscle-specific manner and vary across species, correlating with body size and muscle function.
Contractile Properties of MHC-Based Fiber Types
The contractile properties of muscle fibers correlate with their MHC isoforms. Type I fibers have the lowest shortening velocity, while type IIB fibers have the highest. Hybrid fibers show intermediate properties. Stretch activation kinetics and tension cost also differ among fiber types, contributing to their functional diversity.
Fiber Type Transitions
Muscle fibers can alter their phenotype in response to neuromuscular activity, mechanical loading/unloading, hormonal changes, and aging. Fast-to-slow and slow-to-fast transitions occur sequentially, influenced by factors like neuromuscular activity, mechanical loading, and hormonal levels.
Neuromuscular Activity
Neuromuscular activity plays a significant role in establishing and maintaining muscle fiber phenotypes. Denervation and reinnervation studies demonstrate the impact of neural activity on muscle fiber type transitions. Electrical stimulation models, such as chronic low-frequency stimulation (CLFS), induce fast-to-slow myosin transitions.
Mechanical Loading and Unloading
Mechanical loading induces fast-to-slow transitions, while unloading causes slow-to-fast transitions. Models like stretch-overload and compensatory hypertrophy show increases in slow fibers, whereas unloading leads to increases in fast fibers.
Hormones
Hormones, particularly thyroid hormones, significantly impact muscle fiber type composition. Hypothyroidism induces fast-to-slow transitions, while hyperthyroidism causes slow-to-fast transitions. Testosterone also affects specific muscle fiber compositions.
Aging
Aging leads to fast-to-slow transitions and muscle atrophy. Age-related changes in fiber type composition result from decreases in fast fibers and increases in slow fibers.
Sequence of Myosin Isoform Transitions
MHC isoform transitions follow a sequential pattern from MHCIIb to MHCIb, related to ATPase activities and energy costs. Both fast-to-slow and slow-to-fast transitions involve gradual changes in myosin expression.
Possible Mechanisms Involved in Fiber Type Transitions
Fiber type transitions involve coordinated changes in gene expression, including transcription, translation, and proteolysis. Changes in phosphorylation potential and intracellular Ca2+ levels may trigger these transitions through specific signaling pathways.
Conclusions
Fiber type transitions demonstrate the dynamic nature of skeletal muscle fibers. Future research should focus on elucidating the molecular mechanisms underlying these transitions to better understand muscle plasticity and adaptability.
KEY TERMINOLOGY
Myosin Isoforms: Different forms of the myosin protein, essential for muscle contraction and used to distinguish muscle fiber types.
Skeletal Muscle: A type of muscle tissue responsible for voluntary movements, composed of various fiber types adaptable to different functional demands.
Muscle Fiber Types: Categories of muscle fibers based on contraction speed, fatigue resistance, and specific myosin isoform composition, including slow-twitch (Type I) and fast-twitch (Type II) fibers.
Myosin Heavy Chain (MHC): A major component of the myosin protein, existing in multiple isoforms (e.g., MHCIb, MHCIIa, MHCIId, MHCIIb) that serve as markers for muscle fiber types.
Pure Fiber Types: Muscle fibers expressing a single type of MHC isoform.
Hybrid Fiber Types: Muscle fibers expressing two or more different MHC isoforms, serving as intermediates between pure fiber types.
Neuromuscular Activity: Interaction between nerves and muscles affecting muscle phenotype and function, with changes inducing muscle fiber type transitions.
Mechanical Loading and Unloading: Physical forces applied to muscles causing changes in muscle fiber type composition, with loading referring to increased stress and unloading to reduced stress or inactivity.
Hypothyroidism: A condition characterized by low thyroid hormone levels, inducing fast-to-slow muscle fiber transitions.
Hyperthyroidism: A condition characterized by high thyroid hormone levels, inducing slow-to-fast muscle fiber transitions.
mATPase Histochemistry: A method for identifying muscle fiber types based on the activity of the ATPase enzyme associated with myosin.
Immunohistochemistry: A technique for detecting specific proteins in tissue samples using antibodies, aiding in the identification of muscle fiber types based on their MHC isoform composition.
Electrophoretic Analysis: A laboratory method for separating and analyzing proteins (such as MHC isoforms) based on size and charge, providing detailed information about muscle fiber composition.
Stretch Activation: A property of muscle fibers responding to stretch with an increase in force, varying based on MHC isoform composition.
Tension Cost: The ratio between ATPase activity and isometric tension in muscle fibers, reflecting energy efficiency of different fiber types.
Sarcoplasmic Reticulum Ca2+-ATPase (SERCA): A protein regulating calcium levels in muscle cells, influencing muscle contraction and relaxation.
Calcineurin: A calcium-dependent protein phosphatase involved in signaling pathways regulating muscle fiber type transitions.
Fiber Type Transitions: The process by which muscle fibers change from one type to another in response to stimuli like neuromuscular activity, mechanical loading, hormones, and aging.
Isomyosins: Different combinations of myosin heavy and light chain isoforms within muscle fibers, contributing to muscle tissue functional diversity.
ATP Phosphorylation Potential: The energy state of a muscle fiber indicated by the ATP to ADP ratio, influencing muscle contraction efficiency and fiber type transitions.