48. Muscle Electrophysiology Flashcards
What is the resting membrane potential of a skeletal muscle cell?
Resting membrane potential
skeletal muscle is –90 mV,
nervous tissue is –70 mV and
cardiac muscle is –90 mV
Describe the anatomical structure of a skeletal muscle.
A skeletal muscle is covered
by a connective tissue called the epimysium.
Within the muscle lie thousands of muscle fibres,
which are arranged in bundles or fascicles,
surrounded by perimysium.
These muscle fibres are cylindrical,
multi-nucleated cells,
10–100 μm in diameter and
run along the entire length of the muscle.
They are surrounded by endomysium.
Microscopically, muscle fibres have a striated appearance
due to the presence of numerous myofibrils.
The myofibrils are formed by thick (myosin)
and thin (actin) contractile filaments
in association with the regulatory
proteins tropomyosin and troponin.
These contractile filaments are arranged
within sarcomeres,
which form the basic contractile
unit of a skeletal muscle.
What are the major components of the neuromuscular junction?
Neuromuscular transmission occurs
across the neuromuscular junction,
which is composed of the α-motor neurone,
synaptic cleft and
motor end plate of the muscle fibre.
The end terminals of the motor neurone
are unmyelinated,
with specialised sites for the
storage and release of acetylcholine (ACh).
The motor end plate of the muscle fibre
is deeply folded,
with high concentrations of nicotinic acetylcholine receptors (nAChR)
located at the crests of these folds.
Separating these two components
is the synaptic cleft, a 20 μm gap
containing acetylcholinesterase.
How is acetylcholine synthesised and stored within
the nerve terminal?
ACh is synthesised within the
axoplasm from choline
(obtained from the diet and liver synthesis)
and acetyl coenzyme A (a metabolic by-product)
in a reaction catalysed by
choline-O-acetyltransferase.
Once formed, approximately 80% is
stored in vesicles available for release.
Some of these vesicles (about 1%) lie
at special release sites known as ‘active zones’
and are available for immediate release,
while the others form the ‘reserve pool’,
and are ready for transportation to the release site when needed.
A remaining 20% forms a ‘stationary store’ dissolved in the cytoplasm.
How does neuromuscular transmission occur?
When a motor nerve is depolarised,
voltage-gated Ca2+ channels open in
the presynaptic membrane,
allowing Ca2+ to enter the nerve terminal.
This Ca2+ enables the vesicles
to fuse and release their contents,
by exocytosis.
Approximately 100–200 vesicles
simultaneously release their ACh,
producing an end-plate potential.
When ACh binds to nAChR
(pentameric, ligand gated ion-channels
consisting of 2α, 1β, 1ε and 1δ subunits)
the receptor undergoes a conformational change
and the central ion channel opens
sufficiently to allow the passage of cations, predominantly Na+ and K+.
This causes a localised depolarisation
of the muscle fibre membrane,
which leads to excitation–contraction coupling.
The action of ACh is rapidly terminated by
the presence of acetylcholinesterase
within the synaptic cleft.
When do extra-junctional nAChR appear?
Extra-junctional nAChR rapidly sprout
after denervation and burns injuries.
These receptors are structurally different
as the normal ε subunit is
replaced by the fetal γ subunit.
They are extremely sensitive to depolarising
neuromuscular blocking agents
and the use of these agents can result
in profound hyperkalaemia.
This is why suxamethonium is typically
contraindicated in such patients from 24 hours to 2 years after injury.
In contrast, extra-junctional receptors are relatively resistant to non-depolarising neuromuscular blocking agents and therefore these drugs must be administered at higher doses.
Describe the positive feedback mechanism designed to
increase ACh release.
There are pre-junctional nAChR located on the nerve terminals, which form a positive feedback mechanism designed to increase the release of ACh during periods of high activity (e.g. tetanic stimulation).
These receptors are blocked by non-depolarising neuromuscular blocking drugs
and this explains
why fade on train-of-four stimulation
is observed with these agents.
What is a motor unit?
A motor unit refers to
a single motor neurone
and all the muscle fibres it innervates.
In muscles involved in fine,
precise movement
(e.g. eyes and fingers)
the motor units are small and
one motor neurone innervates only
a few muscle fibres.
This is in sharp contrast to muscles involved in gross, powerful movement where the motor unit consists of a single neurone innervating hundreds of fibres (e.g. quadriceps muscle).
What is excitation–contraction coupling?
This refers to the process by
which the electrical activity of muscle
depolarisation results in
mechanical changes leading to contraction.
As the action potential travels down the T-tubules, which lie very close to the sarcoplasmic reticulum, it triggers calcium release channels (i.e. the ryanodine receptors)
on the sarcoplasmic reticulum to open,
resulting in an influx of intracellular Ca2+.
This Ca2+ binds onto troponin,
bringing about a conformational change in the troponin–tropomyosin complex,
which results in the exposure of the myosin binding sites on the actin filaments.
The myosin heads bind to actin
and perform a ratchet-type movement
towards the centre of the sarcomeres,
dubbed ‘the power stroke’.
AT P then binds onto the myosin head,
allowing it to detach from the actin.
The hydrolysis of this AT P enables the myosin
head to re-orientate itself ready for the next
power stroke.
The muscle relaxes when
intracellular Ca2+ levels decrease.
Rigor mortis occurs due to the lack of AT P,
which prevents the detachment
of the myosin heads from actin and hence the filaments are held in sustained contraction.
In malignant hyperpyrexia there is a defect in the ryanodine receptor, which leads to the uncontrolled release of Ca2+ from within the sarcoplasmic reticulum and hence the sustained muscle contraction and rigidity seen in this condition.
