Histology Ch 11 322-327
Histology of Motor Neurons
Motor Innervation – skeletal muscle fibers are innervated by motor neurons that originate in
spinal cord or brainstem
-Neuromuscular junction is the contact made by terminal branches of axon with muscle fiber
-myelin sheath of axon ends and terminal axon is covered by a thin portion of
neurilemmal (Schwann) cell with its external lamina
-axon ramifies into number of branches which lie in shallow depression on fiber
-axon ending contains numerous mitochondria and vesicles containing acetylcholine
-Release of acetylcholine (ACh) into synapse depolarizes membrane, leading to contraction
-muscle plasma membrane underlies synapse has many junctional folds, and specific
cholinergic receptors for ACh bordering cleft and on top of the folds
-ACh is released into the cleft and binds to nicotinic ACh receptors on sarcolemma of striated
muscle
-the receptor is a transmitter-gated Na channel, where binding of ACh opens Na
channels to cause in influx of Na into striated muscle to cause depolarization
-an enzyme called acetylcholinesterase (AChE) quickly breaksk down acetylcholine to prevent
continued stimulation
-A neuron along with the specific muscle fibers that it innervates is called a motor unit
-single neuron can innervate up to 100 muscle fibers; muscles of fine movement have fewest
fibers per motor unit, such as muscle of eye
-Innervation is necessary for muscle cells to maintain their structural integrity; if nerve to muscle
is disrupted, muscle cell undergoes regressive change known as atrophy – thinning of muscle,
which can regain shape and integrity if innervation is re-established
Events leading to skeletal muscle contraction
1. initiated by impulse along axon of motor neuron when it gets to neuromuscular junction
2. impulse prompts release of ACh into synapse that binds to ACh Na channels for depol.
3. Voltage-gated Na channels open, and Na enters the cell
4. General depolarization spreads via membranes of T tubules, activating voltage sensors
5. At muscle cell triads, T tubules are in close contact with sarcoplasmic reticulum, where
Ca channels are activated by conformational changes of voltage-sensor proteins
6. Ca is rapidly released from sarcoplasmic reticulum into sarcoplasm
7. Ca binds to TnC portion of troponin complex to initiate contraction cycle and Ca is
returned to terminal cisternae of sarcoplasmic reticulum
Sliding filament model states that ratchetlike movements of myosin heads bound to actin
produce movement of thin filaments relative to thick filaments to cause sarcomere shortening
Sensory Innervation – sensory receptors in muscles and tendons are examples of
proprioceptors, which are a part of somatic sensory system providing information about
stretching and shortening of the muscle
-Muscle Spindle – stretch receptor in muscle consisting of 2 types of muscle fibers called spindle
cells and neural terminals, both surrounded by an internal capsule, and a fluid-filled space
separates internal capsule from external capsule
-one spindle cell, the nuclear bag fiber, is multinuclear and transmits degree of stretching
-sensory (afferent, Ia) nerve fibers carry info from muscle spindle and have endings spirally
arranged around midregion of both types of cells
-spindle cells receive motor innervation from brain/spinal cord via γ-motor neurons (efferent),
which regulate sensitivity of stretch receptor
-muscle spindles may also represent axes of functional units within large skeletal muscles by
creating fixation points within muscle substance
-Golgi tendon organs – are found in the tendons of muscle and respond to increased muscle
tension through sensory (afferent Ib) nerve fibers to monitor force of muscle contraction
Myasthenia Gravis – normally, Ach molecules released into synapse at NMJ bind to nicotinic
Ach receptors on sarcolemma, to allow Na to enter cell for action potential  contraction
-after stimulating their own receptors, Ach molecules are degraded by acetylcholinesterase into
acetic acid and choline, which is taken up by axon terminal and reused for Ach synthesis
-in myasthenia gravis, Ach nicotinic receptors are blocked by antibodies against body’s own
protein, thus it is an autoimmune disease resulting in decrease in functional Ach receptors and
loss of junctional folds
-characterized by weakening of muscle fiber response to nerve stimulus, beginning in
extraocular muscles, drooping eyelids, double vision, generalized muscle weakness
-treatment is administration of acetylcholinesterase inhibitors and immunosuppression
Development, Repair, Healing/Renewal – development of myogenic stem cell lineage depends
on expression of regulatory factors
-myoblasts are derived from multipotent stem cells from paraxial mesoderm or mesoderm of
somites (epaxial/hypaxial)
-these cells express MyoD transcription factor, which along with myogenic regulatory
factors (MRFs) activate muscle specific genes and differentiation of all muscle lineages
-balancing effect is through negative regulator myostatin, in the family the bone
morphogenic poritein (BMP) +TGF-B family, and inhibits muscle growth/differentiation
-Skeletal muscle progenitors differentiate into early and late myoblasts
1. Early Myoblasts – form primary myotubes – chainlike structures extending between tendons
of developing muscle, and are formed by synchronous fusion of early myoblasts
-myotubes undergo further differentiation into mature skeletal fibers
2. Late Myoblasts – give rise to secondary myotubes –formed in the innervated zone of
developing muscle where myotubes have direct contact with nerve terminals, and continue to
be formed by sequential fusion of myoblasts into already-formed secondary myotubes at
random positions along their length; smaller diameter and more widely spaced nuclei and an
increased number of myofilaments
-in mature multinucleated fiber, all nuclei are in peripheral sarcoplasm
-some nuclei that appear to belong to skeletal muscle fiber are satellite cells
-Satellite cells are small cells and blend in with muscle sarcoplasm, but has its own nucleus and
are responsible for skeletal muscle’s ability to regenerate (limited)
-these are myogenic precursors of muscle cells normally quiescent and do not express
myogenic regulatory factors, and are activated during injury to form new myoblasts,
which fuse with external lamina to form myotubes
Muscular Dystrophies characterized by degeneration of skeletal muscle fibers, placing demand
on satellite cells to replace them until they are exhausted, in which case additional myogenic
cells are recruited from bone marrow