Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 15 Skeletal Muscle Function
FIGURE 15-1 Excitation of myofibers to contract involves neuromuscular transmission and the subsequent release of calcium
ions into the sarcoplasm. Arrival of an impulse at the axon terminal activates voltage-gated calcium ion channels, resulting
in the influx of calcium ions that initiate the calcium-dependent release of the neurotransmitter acetylcholine (ACh) by
exocytosis. Liberated ACh diffuses across the synaptic cleft to bind with ACh receptors (two molecules of ACh per receptor)
on the postsynaptic sarcolemma. Binding of ACh with AChRs increases the conductance of sodium and potassium ions
across the postsynaptic membrane to produce a local end-plate potential at the neuromuscular junction. The end-plate potential
generates a muscle action potential that spreads away from the neuromuscular junction in all directions over the surface
of the myofiber and into its depths via the transverse (T) tubules. Within the depths of the myofibers, excitation is coupled to
contraction through the release of calcium ions from terminal cisternae of the sarcoplasmic reticulum (SR) through calcium
release channels of the terminal cisternae. The calcium release channels form small “ feet ” that extend from the terminal cisternae
to the T tubules. The liberated calcium ions bind to the regulatory protein troponin and release the inhibitory action of
the regulatory proteins on the contractile events that lead to sliding of the thin (actin) and thick (myosin) filaments. The liberated
ACh is subsequently hydrolyzed by AChE (acetylcholinesterase) within the basal lamina of the synaptic cleft.
transmitters, or changes in voltage and inactivate (close) by
intrinsic regulatory processes. Voltage-gated channels contain
additional voltage-sensing transmembrane domains
and are essential for the generation and modification of
action potentials. Ligand-gated ion channels are essential
for setting myoplasmic calcium concentrations and establishing
signal transduction pathways. Abnormal function
of these ion channels produces muscle weakness or altered
muscle contractions through altered excitability of the
sarcolemma.
The neuromuscular junction or motor end plate is the
synaptic site for chemical transmission of excitation from
the presynaptic axon terminal of a motor neuron to the postsynaptic
skeletal myofiber ( Fig. 15-1 ). The position of the
neuromuscular junction on a muscle fiber can vary among
species, among muscles in a species, and among fibers in
a given muscle. The axon terminal rests within a primary
depression of sarcolemma, the primary cleft, and contains
numerous small vesicles that contain acetylcholine (ACh),
the neurotransmitter for excitation of skeletal myofibers.
Each vesicle contains a quantum of neurotransmitter, consisting
of 6000 to 8000 molecules of ACh. Arising from the
primary cleft underlying the axon terminal are numerous
smaller secondary clefts and complementary folds. The
space within the primary and secondary clefts, located
between the axon terminal and the postsynaptic sarcolemma,
comprises the synaptic cleft. This space is filled with basal
lamina containing acetylcholinesterase (AChE). The synaptic