Nerve, muscle and reflexes
Neurophysiology itself is a huge topic. The aim of this talk is to understand the basics of
nerve transmission, how the junction between nerve and muscle works, and how a simple
reflex arc allows muscle tone to be controlled.
Nerve conduction
There are around 100 billion neurons in the human body. Each cell is specialised to some
degree for the function it performs, but most follow the basic pattern shown below:
The cell body (containing the nucleus) has many short dendrites connecting it to other
neurons, but just one long axon ending in one or more synapses. The synapses may
connect to another neuron’s dendrite, or to muscle.
The electrical nature of nerve conduction was discovered by Galvani in 1791. His muchrepeated experiments using frog sciatic nerve and gastrocnemius muscle showed that the
application of an external electrical current could cause muscle contraction. The
mechanism of physiological nerve and muscle function took much longer to become
clear.
Electrical nerve impulses usually travel in one direction: dendrites - cell body – axon synapse. If an axon is stimulated half way down its length, the signal is propagated in
both directions, toward the synapses and the cell body at the same time. Although
conduction can occur in both directions in an axon, it never does in nature. This is mainly
due to the ‘one way’ property of synapses. Signals arriving at a synapse cause excitation
of nearby nerve or muscle, but activity around a synapse can never trigger a nerve
impulse travelling back towards the cell body.
Nerve conduction actually occurs as a result of sodium and potassium channels in the
nerve membrane opening and closing. Once a critical level of excitation is reached, a
‘wave’ is created travelling down the axon, with each part of the axon stimulating the
next. The travelling wave is call an action potential.
An action potential travelling down an axon is always the same strength – this is known
as the ‘all or none’ principle. The nerve either is transmitting an action potential, or it is
not, and every action potential is the same size. This means that it is the frequency of
action potentials which is key for encoding information, such as how forcefully a muscle
should contract.
In many neurons, axons are sheathed in myelin (formed from the cell membrane of other
cells wrapped around the axon up to 100 times). In beween myelinated areas are small
unmyelinated regions, known as Nodes of Ranvier. These occur every 1mm or so.
Myelination helps speed up conduction in axons – it allows action potentials to ‘jump’
between nodes of Ranvier (known as saltatory conduction). Nerve problems associated
with the disease multiple sclerosis arise due to the destruction of the myelin sheath
(demyelination).
From nerve to muscle
When an action potential arrives at the end of an axon, it triggers neutotransmitter release
from stores (vesicles) in the synapse. The neuroatranmitter (acetylcholine in the case of
skeletal muscle) is released into the synaptic cleft and diffuses across to receptors on the
post-synaptic membrane.
The postsynaptic membrane is folded, to give a large surface area for receptors.
Clinically relevant! In multiple sclerosis, the myelin sheath around axons is destroyed by
an autoimmune reaction. The de-myelinated axons are unable to conduct properly
resulting in neurological problems such as muscle weakness, sensory loss etc.
Clinically relevant! The sodium channels along the axon are the site of action of local
anaesthetics, such as lignocaine. By preventing these channels from opening, pain
impulses are prevented from passing from the periphery to the brain. Unfortunately, the
same channels exist in motor nerves too, so any local anaesthetic placed around a mixed
(sensory and motor) nerve eg. the brachial plexus, will cause a sensory block (desired)
but also a motor block (unwanted).
Clinically relevant! Whilst under anaesthesia, we use drugs which block the acetylcholine
(Ach) receptor to paralyse patients and relax muscle. These drugs (eg. atracurium)
compete with Ach for access to the receptor. When we want to reverse the effects of the
paralysing drug, we use neostigmine, which inhibits the destruction of Ach in the
juntional cleft. Because less Ach is destroyed, more is available to compete for places on
the receptor and normal muscle power returns.
Activation of the Ach receptors at the neuromuscular junction causes a wave of
depolarisation to spread across the muscle. A single action potential lasting 1ms can
cause a muscle contraction of 200ms. Contractions add together if more action potentials
occur in a short time, as there is not long enough for the muscle to relax in between.
Feedback and muscle control
Embedded within muscle itself can be found muscle spindles. These are modified sensory
organs, and transmit impulses when they are stretched. Some muscle spindles react to
degree of stretch, others to speed of movement. They transmit information about muscle
stretch back to the spinal cord.
There is a feedback loop between the spinal cord and the muscle. The cord tells the
muscle to contract (via motor nerves), the muscle contracts and stretches the muscle
spindles, the muscle spindles send signals back to the cord about the strength and speed
of contraction. This loop is commonly known as a reflex arc. It allows fine control over
muscle power to be achieved without any conscious effort. An example would be
balancing bodyweight against gravity when standing up. Here, the power of the extensor
muscles must be altered until the spindles detect no movement at all. The sensitivity of
muscle spindles can be ‘adjusted’ via input from gamma neurons from the cord
Clinically relevant! In upper motor neurone lesions, we see rigidity and an increase in
muscle tone. This occurs because muscle spindles can adjust their sensitivity to stretch by
means of gamma fibres from the spinal cord. In upper motor nerve lesions, it is thought
there is an increase in gamma activity leading to muscle spindles over-reacting and
causing increased muscle tone.
Clinical use of the reflex arc
Clinically relevant! By asking patients to clench their teeth, descending inhibitory
pathways controlling the sensitivity of muscle spindles are inhibited. As the spindles are
now more sensitive, there is a much bigger reaction to muscle stretching (such as might
occur when you use a tendon hammer. The practical upshot is that reflexes become
exaggerated, and more easy to detect!
Group work 1 – Blood gases (normal values will be provided)
1. Look at the following blood gas results and consider the questions below:
pH
pO2
pCO2
BE
7.2
13
4.0
-8.0
On 21% oxygen.
The patient is complaining of a 12 hour history of abdominal pain.
1.
2.
3.
4.
Does the pH show an overall acidosis or an alkalosis?
Is the problem respiratory or metabolic?
What might be happening in the body tissues to cause this problem?
What could the body do to compensate?
2. Look at the following blood gas results and consider the questions below:
pH
pO2
pCO2
BE
7.8
15
2.5
-1.0
On 30% oxygen.
This patient is on a ventilator in the ITU
1.
2.
3.
4.
Does the pH show an overall acidosis or an alkalosis?
Is the problem respiratory or metabolic?
What do you think is causing the problem?
What would the body do if it had control of respiration at this time?
3. Look at the following blood gas results and consider the questions below:
pH
pO2
pCO2
BE
7.35
9.1
7.0
+6.4
This patient is on home oxygen 24% for long standing COPD.
1. The pH appears normal, but what are the respiratory and metabolic components
doing?
2. Which do you think is the underlying problem, and which is compensating?
3. How long does it take for this ‘balance’ to happen?