Lecture 10 - Neuromuscular Junction

Neuromuscular
Junction
KHUSHAL KHAN
D E M O N S T R AT O R C A R D I O LO GY
K H Y B E R M E D I C A L U N I V E R S I T Y – I N S T I T U T E O F PA R A M E D I C A L
SCIENCES
Topic Layout
 Neuromuscular Junction
 Physiological Anatomy of Neuromuscular Junction
 Synthesis & Degradation of Acetylcholine
 Neuromuscular Blockers
 Neuromuscular Stimulants
Neuromuscular Junction
 Neuromuscular junction is the junction between the
terminal branch of nerve fiber and muscle fiber.
 Skeletal muscle fibers are innervated by large
myelinated nerve fibers that originate from large motor
neurons in the anterior horns of the spinal cord.
 Each nerve fiber, after entering the muscle belly,
normally branches and stimulates from three to several
hundred skeletal muscle fibers.
 Each nerve ending makes a junction with the muscle
fiber, called the neuromuscular junction.
 The action potential initiated in the muscle fiber by the
nerve signal travels toward the muscle fiber ends.
Physiological Anatomy of NMJ
 Axon Terminal
 Terminal branch of nerve fiber is called axon terminal.
 When axon comes close to muscle fiber, it looses its
myelin sheath, in such a way that axis cylinder is
exposed.
 This portion of axis cylinder is expanded like a bulb and is
known as motor end plate.
 Axon terminals contain mitochondria and synaptic
vesicles.
 Synaptic vesicles contains neurotransmitter –
Acetylcholine.
 Ach is synthesized by mitochondria of axon terminals
and is stored in synaptic vesicles.
 Mitochondria contains ATP – source of energy for Ach
synthesis.
 Motor End Plate
 The nerve fiber forms a complex of branching nerve terminals
that invaginate into the surface of the muscle fiber but lie
outside the muscle fiber plasma membrane.
 The entire structure is called the motor end plate.
 It is covered by one or more Schwann cells that insulate it from
the surrounding fluids.
 Synaptic Gutter / Synaptic Trough
 The invaginated membrane is called the synaptic gutter or
synaptic trough.
 Synaptic Cleft
 The space between the terminal and the fiber membrane is called
the synaptic space or synaptic cleft.
 It is 20 to 30 nanometers wide.
 Pre-synaptic Membrane
 Membrane of nerve ending is called presynaptic membrane.
 Post-synaptic Membrane
 Membrane of muscle fiber is called postsynaptic membrane.
 Basal Lamina
 It is a thin layer of spongy reticular matrix, through which ECF
diffuses.
 It is present in synaptic cleft.
 An enzyme Acetylcholinesterase is present in large quantities in
the matrix of basal lamina.
 Subneural Clefts
 At the bottom of the gutter are numerous smaller folds of
the muscle membrane (postsynaptic membrane) called
subneural clefts, which greatly increase the surface area at
which the synaptic transmitter can act.
 In the axon terminal are many mitochondria that supply
adenosine triphosphate (ATP).
 ATP is the energy source used for synthesis of a transmitter,
acetylcholine, which excites the muscle fiber membrane.
 Postsynaptic membrane contains receptors called –
Nicotinic Acetylcholine Receptors.
 Acetylcholine (Ach)
 Acetylcholine is used at the neuromuscular junctions, triggering the firing of motor neurons and
affecting voluntary movements.
 Acetylcholine is synthesized in the cytoplasm of the terminal.
 It is absorbed rapidly into many small synaptic vesicles.
 There are about 300,000 of synaptic vesicles present normally in the terminals of a single end plate.
 Acetylcholinesterase (AchE)
 Acetylcholinesterase, also known as acetyl-hydrolase, is the primary cholinesterase in the body.
 It is an enzyme that catalyzes the breakdown of acetylcholine and some other choline esters that
function as neurotransmitters.
 It is found at mainly neuromuscular junctions and in chemical synapses of the cholinergic type, where
its activity serves to terminate synaptic transmission.
Synthesis & Degradation of
Acetylcholine
 Acetylcholine is synthesized in nerve
terminals from acetyl coenzyme A (acetyl
CoA, which is synthesized from glucose) and
choline, in a reaction catalysed by choline
acetyltransferase (CAT).
 In the synaptic space or synaptic cleft are
large quantities of the enzyme
acetylcholinesterase (AchE), which destroys
acetylcholine a few milliseconds after it has
been released from the synaptic vesicles.
Neuromuscular Blockers
 Neuromuscular blockers are drugs which prevent transmission of impulses from nerve fiber to
the muscle fiber through NMJ.
 Neuromuscular blockers are used in anaesthesia during surgery to relax skeletal muscles and
cause paralysis for proper performance of a surgical procedure.
 They are;
 Curare
 Bungarotoxin (snake’s venom)
 Succinylcholine
 Carbamylcholine
 Botulinum Toxin (Clostridium botulinum)
Neuromuscular Stimulants
 Some drugs cause stimulation of NMJ.
 They inhibit acetylcholinesterase so that acetylcholine is not hydrolysed.
 It leads to repeated stimulation of continuous contraction of muscles.
 They are;
 Neostigmine
 Physostigmine
 Di-iso-propyl-fluro-phosphate
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