C H A P T E R 2 8
Neuromuscular junction blocking agents
433
N
erves communicate with muscles at a synapse called
the neuromuscular junction (NMJ). At this point, a
nerve stimulates a muscle to contract. If the nerve is not
able to communicate with the muscle cell, the muscle will
not be able to contract, and paralysis will result. Certain
clinical situations require that a person not be able to
move muscles, including surgery, diagnostic procedures
and mechanical ventilation. Anaesthetics (discussed in
Chapter 27) can prevent muscle movement by suppress-
ing function through the central nervous system (CNS),
with many systemic complications from this depression.
The NMJ-blocking drugs are used to prevent the nerve
stimulation at the muscle cell and cause paralysis of the
muscle directly without total CNS depression and its
many systemic effects.
THE NEUROMUSCULAR JUNCTION
The
neuromuscular junction
is the point at which a
motor neuron communicates with a skeletal muscle fibre.
The end result is muscular contraction. NMJ-blocking
agents affect the normal functioning of muscles by
interfering with the normal processes that occur at the
junction of the nerve and muscle cell.
The functional unit of a muscle, called a
sarcomere
,
is made up of light and dark filaments formed by actin
and myosin molecules. These molecules are arranged in
orderly stacks that give the sarcomere a striated or striped
appearance. Normal muscle function involves the arrival
of a nerve impulse at the motor nerve terminal, followed
by the release of the neurotransmitter acetylcholine
(ACh) into the synaptic cleft. At the
acetylcholine-
receptor site
on the effector side of the synapse, ACh
interacts with the nicotinic cholinergic receptors,
causing depolarisation of the muscle membrane. ACh is
then broken down by acetylcholinesterase (an enzyme),
freeing the receptor for further stimulation. With stimu-
lation, this depolarisation allows the release of calcium
ions, stored in tubules, into the cell. The calcium binds
to troponin, a chemical found throughout the sarcomere.
This binding of troponin releases the actin and myosin
binding sites, allowing them to react with each other. The
actin and myosin molecules react with each other again
and again, sliding along the filament and making it
shorter. This is a contraction of the muscle fibre accord-
ing to the
sliding filament theory
(Figure 28.1). As the
calcium is removed from the cell during repolarisation
of the muscle membrane, the troponin is freed and once
again prevents the actin and myosin from reacting with
each other. The muscle filament then relaxes or slides
back to the resting position.
A dynamic balance of excitatory and inhibitory
impulses to the muscle results in muscle tone. However,
if ACh cannot react with the cholinergic muscle receptor
or if the muscle cells cannot repolarise to allow new
A
Muscle relaxed—no
contact between
actin and myosin
B
Cross-bridges form,
actin filaments move
closer together
C
Cross-bridges return
to normal postion,
attach to new sites
Sarcomere
Contraction
Contraction
Actin filaments
Myosin heads
Cross-bridges
Myosin filaments
FIGURE 28.1
Sliding filament mechanism of skeletal muscle contraction.
A.
Muscle is relaxed, and there is no contact between the actin and
myosin filaments.
B.
Cross-bridges form, and the actin filaments are moved closer together as the muscle fibre contracts.
C.
The cross-bridges
return to their original position and attach to new sites to prepare for another pull on the actin filaments and further contraction.
