What is Skeletal Muscle?
Tue, 3 Nov 2009
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system. It is one of three major muscle types, the others being cardiac and smooth muscle. As its name suggests, skeletal muscle is linked to bone by bundles of collagen fibers known as tendons.
Skeletal muscle is made up of individual components known as muscle fibers. These fibers are formed from the fusion of developmental myoblasts. The myofibers are long, cylindrical, multinucleated cells composed of actin and myosin myofibrils repeated as a sarcomere,
the basic functional unit of the cell and responsible for skeletal
muscle's striated appearance and forming the basic machinery necessary
for muscle contraction. The term muscle refers to multiple bundles of
muscle fibers held together by connective tissue.
Individual muscle fibers are formed during development from the
fusion of several undifferentiated immature cells known as myoblasts
into long, cylindrical, multi-nucleated cells. Differentiation into
this state is primarily completed before birth with the cells
continuing to grow in size thereafter. Skeletal muscle exhibits a
distinctive banding pattern when viewed under the microscope due to the
arrangement of cytoskeletal elements in the cytoplasm of the muscle fibers. The principal cytoplasmic proteins are myosin and actin (also known as "thick" and "thin" filaments, respectively) which are arranged in a repeating unit called a sarcomere. The interaction of myosin and actin is responsible for muscle contraction.
There are two principal ways to categorize muscle fibers: the type of myosin (fast or slow) present, and the degree of oxidative phosphorylation
that the fiber undergoes. Skeletal muscle can thus be broken down into
two broad categories: Type I and Type II. Type I fibers appear red due
to the presence of the oxygen binding protein myoglobin. These fibers are suited for endurance and are slow to fatigue because they use oxidative metabolism
to generate ATP. Type II fibers are white due to the absence of
myoglobin and a reliance on glycolytic enzymes. These fibers are
efficient for short bursts of speed and power and use both oxidative
metabolism and anaerobic metabolism depending on the particular sub-type. These fibers are quicker to fatigue.
Cellular physiology and contraction
In addition to the actin and myosin components that constitute the sarcomere, skeletal muscle fibers also contain two other important regulatory proteins, troponin and tropomyosin,
that are necessary for muscle contraction to occur. These proteins are
associated with actin and cooperate to prevent its interaction with
myosin. Skeletal muscle cells are excitable and are subject to depolarization by the neurotransmitter acetylcholine, released at the neuromuscular junction by motor neurons.
Once a cell is sufficiently stimulated, the cell's sarcoplasmic reticulum releases ionic calcium
(Ca2+), which then interacts with the regulatory protein troponin.
Calcium-bound troponin undergoes a conformational change that leads to
the movement of tropomyosin, subsequently exposing the myosin-binding
sites on actin. This allows for myosin and actin ATP-dependent
cross-bridge cycling and shortening of the muscle.
Muscle force is proportional to physiologic cross-sectional area (PCSA), and muscle velocity is proportional to muscle fiber length.
The strength of a joint, however, is determined by a number of
biomechanical parameters, including the distance between muscle
insertions and pivot points and muscle size. Muscles are normally
arranged in opposition so that as one group of muscles contract,
another group relaxes or lengthens. Antagonism in the transmission of
nerve impulses to the muscles means that it is impossible to stimulate
the contraction of two antagonistic muscles at any one time. During
ballistic motions such as throwing, the antagonist muscles act to
'brake' the agonist muscles throughout the contraction, particularly at
the end of the motion. In the example of throwing, the chest and front
of the shoulder (anterior Deltoid) contract to pull the arm forward,
while the muscles in the back and rear of the shoulder (posterior
Deltoid) also contract and undergo eccentric contraction to slow the
motion down to avoid injury. Part of the training process is learning
to relax the antagonist muscles to increase the force input of the
chest and anterior shoulder.
Signal transduction pathways
Skeletal muscle fiber-type phenotype in adult animals, and probably
people, is regulated by several independent signaling pathways. These
include pathways involved with the Ras/mitogen-activated protein kinase
(MAPK), calcineurin, calcium/calmodulin-dependent protein kinase IV,
and the peroxisome proliferator γ coactivator 1 (PGC-1). The Ras/MAPK
signaling pathway links the motor neurons and signaling systems,
coupling excitation and transcription regulation to promote the
nerve-dependent induction of the slow program in regenerating muscle.
Calcineurin, a Ca2+/calmodulin-activated phosphatase implicated in
nerve activity-dependent fiber-type specification in skeletal muscle,
directly controls the phosphorylation state of the transcription factor
NFAT, allowing for its translocation to the nucleus and leading to the
activation of slow-type muscle proteins in cooperation with myocyte
enhancer factor 2 (MEF2) proteins and other regulatory proteins.
Calcium-dependent Ca2+/calmodulin kinase activity is also upregulated
by slow motor neuron activity, possibly because it amplifies the
slow-type calcineurin-generated responses by promoting MEF2
transactivator functions and enhancing oxidative capacity through
stimulation of mitochondrial biogenesis.
Contraction-induced changes in intracellular calcium or reactive
oxygen species provide signals to diverse pathways that include the
MAPKs, calcineurin and calcium/calmodulin-dependent protein kinase IV
to activate transcription factors that regulate gene expression and
enzyme activity in skeletal muscle.
a transcriptional coactivator of nuclear receptors important to the
regulation of a number of mitochondrial genes involved in oxidative
metabolism, directly interacts with MEF2 to synergistically activate
selective ST muscle genes and also serves as a target for calcineurin
signaling. A peroxisome proliferator-activated receptor δ
(PPARδ)-mediated transcriptional pathway is involved in the regulation
of the skeletal musclefiber phenotype. Mice that harbor an activated
form of PPARd display an “endurance” phenotype, with a coordinated
increase in oxidative enzymes and mitochondrial biogenesis and an
increased proportion of ST fibers. Thus—through functional
genomics—calcineurin, calmodulin-dependent kinase, PGC-1α, and
activated PPARδ form the basis of a signaling network that controls
skeletal muscle fiber-type transformation and metabolic profiles that
protect against insulin resistance and obesity.
The transition from aerobic to anaerobic metabolism during intense
work requires that several systems are rapidly activated to ensure a
constant supply of ATP for the working muscles. These include a switch
from fat-based to carbohydrate-based fuels, a redistribution of blood
flow from nonworking to exercising muscles, and the removal of several
of the by-products of anaerobic metabolism, such as carbon dioxide and
lactic acid. Some of these responses are governed by transcriptional
control of the FT glycolytic phenotype. For example, skeletal muscle
reprogramming from an ST glycolytic phenotype to an FT glycolytic
phenotype involves the Six1/Eya1 complex, composed of members of the
Six protein family. Moreover, the Hypoxia Inducible Factor-1α (HIF-1α)
has been identified as a master regulator for the expression of genes
involved in essential hypoxic responses that maintain ATP levels in
cells. Ablation of HIF-1α in skeletal muscle was associated with an
increase in the activity of bob-limiting enzymes of the mitochondria,
indicating that the citric acid cycle and increased fatty acid
oxidation may be compensating for decreased flow through the glycolytic
pathway in these animals. However, hypoxia-mediated HIF-1α responses
are also linked to the regulation of mitochondrial dysfunction through
the formation of excessive reactive oxygen species in mitochondria.
Other pathways also influence adult muscle character. For example,
physical force inside a muscle fiber may release the transcription
factor Serum Response Factor (SRF) from the structural protein titin,
leading to altered muscle growth.
Research on skeletal muscle properties uses many techniques. Electrical muscle stimulation
is used to determine force and contraction speed at different
stimulation frequencies, which are related to fiber-type composition
and mix within an individual muscle group.