Lecture

11 Muscle II – September 29, 2017 (Dr. Moukhles)

Ch 8:
3rd edition: pg. 168-184
4th edition: pg. 192-209

Somatic/Voluntary Motor Neuron Innervation
• Skeletal muscle: under voluntary control by motor neurons
• Motor unit: a motor neuron that originates in the ventral portion of the
spinal cord and all the muscle fibers that it innervates
• Neuromuscular junction (NMJ): the junction between the axon terminal of
the motor neuron and the motor endplate of the myofiber
o Axon terminal: the presynaptic portion of the NMJ and sends the
synaptic signal
o Motor endplate: the postsynaptic portion of the NMJ that receives the
synaptic signal. It is a specialized area of the sarcolemma/plasma
membrane of the skeletal myofiber
o Synaptic cleft: The depression in the sarcolemma of the myofiber
caused by the presence of the motor endplate
o Junctional folds: folds of the plasma membrane at the NMJ
Excitation-Contraction Coupling
• An action potential traveling down the axon of the neuron will depolarize the
neuronal plasma membrane
• Presynaptic vesicles containing the neurotransmitter, acetylcholine (ACh),
fuse with the plasma membrane of the axon terminal
• ACh is released into the synaptic cleft where it binds ACh receptors on the
sarcolemma of the motor end plate
• This triggers a depolarizing action potential in the muscle plasma membrane
that travels down the T-tubules to induce Ca++ release from the terminal
cisternae of the SR in the triad (10Lect – Muscle 1)
• The result is a contraction of the sarcomeres
• Contractions stop due to the action of an ATP-dependent Ca++ pump in the
SR
o Actively transports the released Ca++ in the cytoplasm back into the
SR
Please note: The motor neurons that are involved in this process are induced to
differentiate in the ventral portion of the developing spinal chord due to the
inductive action of the notochord as will be discussed in the Development lectures;
the specifics of neuron structure and function will be discussed in more detail in the
Nervous tissue lectures

Clinical correlations:
1) Botulism
• A multimeric toxin produced by the bacterium Clostridium botulinum that
prevents the release of ACh from axon terminals by inhibiting the fusion of
ACh-containing vesicles with the pre-synaptic axonal membrane at the NMJ
 • Large quantities of botox leads to botulism à characterized by large scale
muscular paralysis, respiratory failure, and even death because muscle
contraction can’t occur
• For cosmetic purposes it is used in much smaller doses to paralyze muscle
contraction in order to decrease age-related wrinkling
2) Duchenne and Becker Muscular Dystrophy
• Disease that causes weakness and loss of muscle.
• Generally hereditary or result from mutations early at birth
- Caused by mutations in the cytoskeletal linker protein dystrophin
o Dystrophin is a vital part of the dystroglycan protein complex (See
Lect10 Muscle I). This complex acts as a linkage between the ECM and
the cytoskeleton via intracellular actin
- Mutations in dystrophin cause the complex to be released from the actin
cytoskeleton intracellularly.
o This disrupts the link of the muscle fibers to the basal lamina. Over
time this will cause damage to the sarcolemma and destruction of the
sarcomeres, ultimately leading to myofiber/muscle cell death. This
will induce inflammation (increased macrophages), followed by
increased collagenous CT and adipose tissue infiltration into the
muscle—known as fatty fibrosis.
o At the gross anatomical level this results in an initial swelling of the
muscle = pseudo-hypertrophy. This is followed by a gradual 'muscle
wasting' (i.e. loss of muscle mass/definition).
o Secondary effects are scholiosis (lateral curvature of the spine),
difficulties with clearing the respiratory tract and cardiac problems
• Attempts to correct the defect are being made using viral-mediated transfer of
the wild-type dystrophin gene into myofibers.

(Note: True 'hypertrophy' is an increase in tissue/organ size that is usually caused by
an increase in the size of the functional cells in the tissue/organ. Thus, the increased
muscle mass that occurs due to exercise in a healthy person is true hypertrophy as
opposed to the fake/pseudo hypertrophy that is a clinical symptom in DMD that is
caused by an increase in inflammation and fibrosis not an increase in actual myofiber
cell mass)
Inflammation will be described in some detail in the Lymphoid lectures.

Cardiac Muscle
• Found exclusively in the heart
• Cardiac muscle cells = cardiac myofibers = cardiomyocytes form the
'myocardium' (ie. the thick contractile walls of the heart's ventricles and the
atria).
• Cardiac myofibers are striated with true sarcomeres but they are mononuclear
(one central nucleus per cardiac myofiber/cardiac muscle cell)
• Contraction is involuntarily controlled (fibers contract spontaneously with
inherent rhythmicity).
• Cardiac myofibers are short and branched and they attach to each other by
intercalated disks that contain:
1) Transversely-located (across the fibers at right angles) adherens junctions
that are adhesive and anchor actin myofilaments of the terminal sarcomeres.
There are also desmosomes that anchor the adjacent cardiomyofibers to each
other.
2) Laterally-located (parallel to the myofilaments) gap junctions, which
electrically couple the cardiac myofibers by allowing for rapid flow of
information between fibers.
- This is important for the inherent rhythmicity of cardiomyocytes, as
the stimulation of one cell can lead to the stimulation of neighbouring
cells via gap junction transfer of ions.
• T tubules are present and prominent in cardiomyocytes. However, they have
sparse amounts of sarcoplasmic reticulum associated with them compared to
the situation in skeletal myofibers.
o Dyad/diad: One tubule usually has one associated cistern of sarcoplasmic
reticulum (dyad in cardiomyocytes vs triad in skeletal muscle).
• In cardiac muscle not as much calcium is stored in the sarcoplasmic reticulum,
therefore more calcium enters the cells to initiate contraction through coupled
calcium-sodium channels in the T-Tubule membrane as well as the sarcoplasmic
reticulum membrane.

Smooth Muscle
• Found in the walls of tube-based organs/structures where their contraction
decreases the diameter of the central lumen (eg. during rhythmic, peristaltic
contractions in the gastrointestinal and urogenital systems; to decrease blood
flow through small arteries and arterioles)
• Smooth muscle myofibers are mononucleated, spindle-shaped and tapered at
each end.
o There are no T-Tubules
• Contraction is involuntary and is initiated by multiple contacts from the axons
of neurons from the autonomic nervous system
o There are no well-defined neuromuscular junctions
• There are large numbers of gap junctions between smooth muscle myofibers to
allow direct electrical communication between adjacent smooth muscle fibers.
o This direct electrical communication facilitates slow rhythmic
contractions across many linked myofibers in smooth muscle tissues
§ Every individual smooth myofiber/muscle cell does not need
to be innervated to contract due to the gap junction-mediated
electrical coupling with neighbouring myofibers.
• There are no sarcomeres; therefore smooth muscle is not striated.
• Smooth myofibers have an extensive array of interweaving thin (actin) and
thick (myosin) filaments that give some multi-directionality to the contraction
(ie. they are arranged at oblique angles rather than in parallel arrays as is the
case in skeletal and cardiac myofiber sarcomeres).
 o Thin filaments attach to aggregates of adapter/scaffold/linker proteins
called dense bodies that include actin bundling proteins (eg. alpha-
actinin) and act as an anchor for the filaments within the cytoplasm
(analagous to Z-lines/Z-plaques in skeletal/cardiac muscle).
o Actin filaments are also bundled and anchored to dense plaques at focal
adhesions at the plasma membrane.
• Contractile units consist of myosin filaments connecting to the actin filaments:
o Thick filaments (myosin) act on thin filaments to cause contractions
between the dense bodies and dense plaques (brings them closer
together); this leads to shortening of the long, tapered, fusiform-shaped
cells as well as some cell twisting. In histological sections this contractile
twisting causes the nuclei to take on a 'corkscrew'-like appearance.
o a meshwork of intermediate filaments also courses through the
smooth muscle fibers
o Examples of sites of smooth muscle:
§ Arteries and veins: in some of these blood vessels they are found in the
central tunica media (Cardiovascular lecture for more detail)
§ Multiple layers in the wall of the stomach and intestines: that act together
to generate peristalsis (progressive and rhythmic contractions of the
smooth muscle that propel food through the digestive tract; see
Gastrointestinal lectures for more detail).

Please note: these arrangements of smooth muscle tissues will be discussed in detail
in the Circulatory and Gastrointestinal System lectures.