2. • all skeletal muscles is under voluntary or reflex control by
motor neurons
• a motor nerve fiber divides into several branches
• each branch of the motor nerve fiber innervates one
muscle fiber
• each single motor neuron & the muscle fibers it
innervates is called a motor unit
• The junction between a motor nerve fiber & a muscle
fiber is known as the neuromuscular junction.
3.
4.
5. presynaptic portion of neuromuscular junction
• as the axon of motor neuron approaches the muscle
fiber, it loses its myelin sheath & divides extensively into
several fine branches- axon terminal
• terminal is covered by Schwann cells
• each terminal is expanded at its end to form a knobby
structure- synaptic knob (terminal bottom)
• terminal bottom lies in the groove (synaptic trough) in
the surface of muscle fiber
• vesicles are clustered around specific points- active zones
6. synaptic cleft
• gap between the terminal bottom & the muscle fiber,
which is about 20-30 nm wide
• muscle fiber is covered by basement membrane or basal
lamina, consisting of collagen, glycoproteins & other
extracellular matrix proteins (neurexins)
• also contain acetylcholinesterase
7. postsynaptic portion of neuromuscular junction
• the part of the sarcolemma that lies directly under the
terminal button known as end-plate membrane (motor
end-plate)
• invaginated membrane is called the synaptic gutter or
synaptic trough
• at the bottom of the gutter are numerous smaller folds of
the muscle membrane- subneural clefts
– contains numerous Ach receptors
8.
9.
10.
11.
12. Ach receptor
• ACh receptor are nicotinic type
• each receptor is a protein complex (molecular weight of
275,000)
• composed of two α & one each of β, δ, & γ
• channel remains constricted until 2 Ach molecules attach
respectively to the 2 α subunit proteins
– this causes a conformational change that opens the channel
13.
14. A, Weakened end plate potential recorded in a curarized muscle
B, Normal end plate potential
C, Weakened end plate potential caused by botulinum toxin
15. • several deadly toxins which block neurotransmitter
release
• tetanus toxin & botulinum toxins B, D, F, & G act on
synaptobrevin, & botulinum toxin C acts on syntaxin
• botulinum toxins A & B act on SNAP-25
• on the positive side, local injection of small doses of
botulinum toxin ("botox") has proved effective in the
treatment of a wide variety of conditions
– injection into the lower esophageal sphincter to relieve achalasia
– injection into facial muscles to remove wrinkles
16. Drugs that stimulate the muscle fiber by acetylcholine-like action
• methacholine, carbachol, & nicotine, have the same effect on
the muscle fiber as does acetylcholine
• drugs are not destroyed by cholinesterase or are destroyed so
slowly that their action often persists for many minutes to
several hours
Drugs that stimulate the neuromuscular junction by inactivating
acetylcholinesterase
• neostigmine & physostigmine inactivate acetylcholinesterase for
up to several hours
• diisopropyl fluorophosphate inactivates acetylcholinesterase for
weeks
Drugs that block transmission at the neuromuscular junction
• a group of drugs known as curariform drugs can prevent
passage of impulses from the nerve ending into the muscle
• D-tubocurarine blocks the action of acetylcholine on the muscle
fiber acetylcholine receptors
17. Myasthenia gravis
• occurs in about 1 in every 20,000 persons
• patients have developed immunity against their own
acetylcholine-activated ion channels
• the end plate potentials that occur in the muscle fibers are
mostly too weak to stimulate the muscle fibers
• if the disease is intense enough, the patient dies of paralysis
(paralysis of the respiratory muscles)
• disease usually can be ameliorated for several hours by
administering neostigmine or some other anticholinesterase
drug
18. Lambert–Eaton Syndrome
• muscle weakness is caused by an autoimmune attack
against Ca2+ channels in the nerve endings
• proximal muscles of the lower extremities are primarily
affected, producing a waddling gait & difficulty raising
arms
• about 40% of patients with LEMS also have cancer,
especially small cell cancer of the lung
• a syndrome similar to LEMS can occur after the use of
aminoglycoside antibiotics, which impair Ca2+ channel
function
19.
20. References
• Textbook of Medical Physiology, 12/E Guyton &
Hall
• Ganong Review of Medical Physiology, 23/E