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Mechanisms of Nerve Conduction
1. List the ion channels and ionic fluxes involved in the phases of an action
potential.
Neurons are highly irritable (responsive to stimuli). When a neuron is adequately stimulated, an
electrical impulse is generated and conducted along the length of the axon. This response is an
action potential or a nerve impulse. This response is always the same regardless of the source or the
type of stimuli.
Basic principles of electricity
The human body is electrically neutral – same number of positive and negative charges. There are
areas where one type of charge predominates. Energy is used to separate these opposite charges.
The coming together of charges liberates energy that can be used. Situations where there is
separated electrical charges of opposite sign have potential energy.
The role of ion channels in the membrane
Ion channels are made up of membrane proteins scattered throughout the plasma membrane. Some
of these channels are always open (passive or leakage channels). Others are active or gated
Chemically gated or ligand gated channels are open when the appropriate (neurotransmitter) binds
Voltage-gated channels open and close in response to changes in the membrane potential.
Mechanically gated channels open in response to physical deformation of the receptor (touch and
pressure receptors).
Ions move along an electrical gradient when they move toward an area of opposite charge.
Ions move along a chemical gradient when they move from an area of higher concentration to an
area of lower concentration.
Both the electrical and chemical gradient = electrochemical gradient.
The resting membrane potential
Neurons have a resting membrane potential of -70mV which indicates that the cytoplasmic side
(inside the cell) is negatively charged relative to the outside. The membrane is also said to be
polarised. The resting membrane potential varies from -40mV to -90mV in different neurons.
This resting potential exists only across the membrane; all other solutions are electrically neutral.
The resting membrane potential is generated by the differences in ionic make up of the intra and
extracellular fluids and the different permeability of the plasma membrane to these ions.
Potassium plays the most important role in generating the membrane potential. K⁺ ions diffuse out
of the cell along their concentration gradient much more easily and quickly than Na⁺ can enter along
theirs. K⁺ loss from the cell continues until the force of its concentration gradient is balanced by the
pull created by the negativity, leading to a resting membrane potential being achieved.
The sodium-potassium pump, driven by ATP maintains the resting membrane potential by ejecting 3
Na⁺ from the cell and transporting 2 K⁺ back into the cell.
There are 2 types of signals:

Graded potential – signals over short distances

Action potentials (AP) – signals over longer distances
Depolarisation is a reduction in membrane potential. The inside of the membrane (intracellular side)
becomes less negative (closer to zero) than the resting potential, e.g. -70mV to -65mV is a
depolarisation. Also includes when the membrane potential moves above zero. Depolarisation
produces nerve impulses.
Hyperpolarisation is when the membrane potential increases, becoming more negative than the
resting potential, e.g. -70mV to -75mV is hyperpolarisation. It reduces the likelihood of a nerve
impulse being generated.
Action Potentials
Only cells with excitable membranes (neurons and mm cells) can generate an AP. The sequence of
events: depolarisation → repolarisation → hyperpolarisation (slight). Occurs over milliseconds.
Unlike graded potentials, AP’s don’t decrease in strength with distance. The events of an AP is the
same in skeletal mm cells and in neurons.
In neurons, only axons can generate an AP.
The neurons transmits an AP only when adequately stimulated. The stimulus changes the
permeability of the neuron’s membrane by opening specific voltage-gated channels on the axon. The
channels open and close in response to changes in the membrane potential and activated by local
currents (graded potentials). The transition from graded potential to AP occurs at the axon hillock.
Generation of an AP – involves 3 consecutive but overlapping changes in the membrane
permeability induced by depolarisation of the axonal membrane.
1. Resting state: voltage-gated channels are closed
Na⁺ and K⁺ channels are closed but small amounts of K⁺ leave via leakage channels and smaller
amount of Na⁺ diffuse in.
Each Na⁺ channel has 2 voltage sensitive gates

Activation gate – closed at rest and responds to depolarisation by opening rapidly

Inactivation gate – open at rest and responds to depolarisation by slowly closing.
Depolarisation opens then closes the Na⁺ channels. Both need to be open for Na⁺ to enter but
closing either closes the channel.
Each active potassium channel has a single voltage gate which is closed at rest and opens slowly
during depolarisation.
2. Depolarising phase: ↑ in Na⁺ permeability and reversal of the membrane potential
Depolarisation of axonal membranes by local currents causes the Na⁺ channel gates to quickly open
and Na⁺ rushes into the cell.
The influx of positive charge depolarises that local patch of membrane, opening more activation
gates so the cell interior becomes less negative.
Once depolarisation reaches a certain threshold level (-50mV and -55mV), it becomes self generating
and driven by positive feedback. As more Na⁺ enters, the depolarisation of the membrane opens
more activation gates until all the Na⁺ channels are open. At this point Na⁺ permeability is 1000
times greater than a resting neuron.
The resting membrane potential becomes less and less negative and actually becomes positive
(+30mV) as Na⁺ rushes in along its electrochemical gradient. This rapid depolarisation produces a
sharp upward spike of the AP.
Membrane permeability depends on membrane potential and membrane potential depends on
membrane permeability. This is because ↑Na⁺ permeability due to ↑channels opening leads to
greater depolarisation which leads to ↑Na⁺ permeability etc. This phase is responsible for the
‘action’ in AP.
3. Repolarising phase
a. Decrease in Na⁺ permeability
The depolarising phase lasts only 1ms and is self limiting. As the membrane potential passes 0mV
and becomes positive, the positive intracellular charge resists further Na⁺ entry.
Also the slow inactivation gates of the Na⁺ channels begin to close after a few milliseconds of
depolarisation therefore the membrane permeability to Na⁺ declines to resting levels, and then it
completely stops. The AP spike stops rising and reverses direction.
b. Increase in K⁺ permeability
As Na⁺ entry declines, the slow voltage K⁺ gates open and K⁺ rushes out of the cell, following its own
electrochemical gradient. This leads to restoration of internal negativity of the neuron. Both the
abrupt decline in Na⁺ permeability and the increased permeability to K⁺ contribute to repolarisation.
4. Hyperpolarisation: K⁺ permeability continues
K⁺ gates are slow to respond to the depolarisation signal, the period of increased K⁺ permeability
lasts longer than is needed to return the membrane to resting state.
This excessive K⁺ efflux, an after hyperpolarisation, causes a slight dip in the AP curve before the K⁺
gates close.
At this time, the activation and inactivation gates of Na⁺ are closed therefore the neuron is
insensitive to a stimulus and depolarisation at this time.
Repolarisation restores resting electrical conditions, the sodium-potassium pump restores ion
distribution.
It might appear that large amounts of Na⁺ and K⁺ are exchanged but in reality, it is only a small
amount. The axonal membrane has thousands of Na⁺ and K⁺ pumps so ionic changes can be quickly
corrected.
2. Indicate how action potentials are initiated and propagated
Propagation of an AP - unmyelinated fibres
To serve as the neuron’s signalling device, an AP must be propagated (sent or transmitted) along the
axon’s entire length.
The AP’s generated by the influx of Na⁺, through a given area of membrane, this establishes local
currents that depolarise adjacent membrane areas in a forward direction (away from origin).
The area where the AP originated has just generated an AP, the Na⁺ gates are closed and no new AP
is generated there, therefore the AP propagates away from its point of origin. If an isolated axon is
stimulated or an axon is stimulated at a node of Ranvier, the nerve impulse will move away in all
directions from the stimulus along the membrane.
In the body, AP’s are initiated at one end of the axon and conducted to the terminals. Once initiated,
an AP is self propagating and continues at a constant velocity – like a dominoes effect.
At each segment, depolarisation is followed by repolarisation which restores resting membrane
potential. The membrane potential is regenerated anew at each membrane patch and each
subsequent AP is identical to the initial one.
Propagation of an AP – myelinated fibres
Myelin sheaths increase the rate of impulse propagation because myelin acts as an insulator to
prevent all leakage charge from the axon.
Current can pass through the membrane at the nodes of Ranvier. All voltage gated Na⁺ channels are
concentrated here.
When an AP is generated, the depolarisation doesn’t dissipate through adjacent membrane regions
but is maintained and moved onto the next node, where it triggers another AP. This is called
salutatory conduction because it leaps from one node to the next. Offers faster conduction.