Nerve Signals:
Action Potentials
Resting Potential
‘Resting’ refers to the neuron not conducting a signal (not
conducting an action potential).
Inactive (non-signaling) neurons maintain an electrical
potential (a relative voltage difference) across their
axomembranes of ~ -65 mV. Axomembranes are said to be
polarized. By convention, the ECF voltage is called zero.
• This indicates that, relatively speaking, the inside of the
axon is more negative (or less positive) in charge than the
outside of the axon (ECF).
• Such a potential is measured by an oscilloscope, which is a
fancy voltmeter designed to test neurons.
• The difference in charge (electrical potential or axomb
polarization) is attributable to a number of factors:
In no particular order of importance:
i. A Na+/K+ pump (carrier protein) maintains an unequal
distribution of Na+ and K+ across an axomembrane – there
exists a higher [Na+] outside the neuron (in the ECF), and a
higher [K+] inside the neuron (in the axoplasm). This, in
itself, does not contribute to the negative cell potential, but
the fact that the pump actively moves 3 Na+ out for every 2
K+ in (this is done primarily after nerve signals to reset the
neuron) contributes to there being, at any one time, more
cations outside than inside the neuron; thus contributing to
the relative negative polarity across the axomembrane. The
pump, which moves these ions against their concentration
gradients, serves to maintain the steep concentration
gradients mentioned with respect to Na+ and K+ (important
for nerve signals).
ii. Na+ and K+ possess specific channel proteins (more for K+)
that allow for a slow leakage of ions down their
concentration gradients. K+ leaks out about 50x faster than
Na+ leaks in  promotion of negative resting potential
(there are very few of these ‘open’ channels compared to
the soon-to-be-mentioned ‘gates’ that open during an action
potential). The pump acts to continuously correct leakage.
iii. There exist plenty of large anions within the neuron
(proteins, amino acids, sulfate, phosphate), which cannot
move out of the cell (either too large or possessing no
specific channel proteins), thus creating a perpetual
contribution of negative charge inside.
iv. The [Cl-] is greater outside than inside (which might have
you wondering…), but at least there is some (albeit much
less than outside) Cl- inside; this, in contrast with the large
anions mentioned in (iii), where they only exist inside the
cell. See fig. 17.4(a) p. 325.
Methods of Ion Transfer Across Axomembrane
1. Channel Protein Diffusion: this refers to the leakage of
Na+ and K+ ions;
2. Active Transport – Na+/K+ Pump: moves ions against
their conc. gradients to ‘reset’ neuron for another action
potential (ie. re-creates steep gradients mentioned earlier);
3. Protein Gates (Diffusion): specific, one-way proteins
(gates) – two types: Na+ gates (open to allow Na+ into
axon (down its conc. gradient)), K+ gates (open to allow
K+ out of axon (down its conc. gradient)) – these will be
discussed in detail during analysis of action potentials;
however, it is important to point out that these gates, when
opened, serve as the primary mechanism by which Na+
and K+ move into/out of the neuron as they vastly
outnumber the ‘always open’ channels mentioned earlier.
An action potential requires a flood of ions in either
direction – thus the need for the numerous gates.
Action Potential (the SIGNAL!)
• The signal transmitted along the length of a neuron,
from a dendrite, cell body, or axon hillock to the
synaptic endings of an axon, is an electrical signal
that depends on a rapid, localized flow of ions
across the neuron’s mb.
• This signal (flow of ions across the mb) then travels
in a perpendicular direction along a neuron
(‘domino’ effect).
• All cells possess a membrane potential of some
kind, but only neurons (and muscle cells) have the
ability to generate changes in that potential (and
thus, generate a signal).
• A stimulus is received by a dendrite (or a cell body); the
stimulus can be pressure, temperature, light (eyes), or
chemical and it is received by specific receptors on the
dendrites.
• Chemical stimuli usually come from other neurons, whereas the
other stimuli arise from the environment.
• The stimulus is passed to the cell body, which then
integrates it. If the stimulus is ‘weak’, it will not reach the
axon hillock; if it is ‘medium’-‘strong’, it is passed on to the
axon hillock.
• If the stimulus is strong enough, it will cause the
axomembrane of the axon hillock to depolarize to a certain
degree (ie. the axoplasm will become less negative in
charge). If that certain degree of depolarization reaches a
certain threshold, an action potential (AP) will result.
• How does the depolarization occur? See fig. 17.4(b) p.325
Steps: 1. Resting Potential – as described earlier…
2. DEPOLARIZATION -- stimulus reaches axon hillock and
causes Na+ gates to open. A stronger stimulus initially
opens more gates, and vice versa. This allows Na+ to
move into the axoplasm (across the axomembrane) down
its concentration gradient (and due to the fact that the
axoplasm is negative in charge compared to Na+’s charge
– opposites attract!). If the stimulus is strong enough,
threshold potential will be reached (-55mV to –40mV,
depending on text; we’ll go with our text (-40mV)) and
ALL remaining Na+ gates open (example of positive
feedback) so that Na+ floods the axoplasm. Na+
equilibrium (with respect to charge and concentration) is
reached when the potential across the axomembrane
(axoplasm charge) equals +40mV. Depolarization (APs)
are referred to as ‘All-or-None’ meaning that threshold is
either reached, or not reached.
• So, if the stimulus is not strong enough to open a
sufficient amount of Na+ gates, threshold will NOT
be attained, and the signal ‘dies’.
3. REPOLARIZATION – once Na+ equilibrium is
attained, the Na+ gates close. This signals K+ gates
to open and K+ floods OUT of the axoplasm into the
ECF (due to conc. gradient and electrical gradient).
K+ equilibrium is attained at ~ -80-85mV (called the
‘undershoot’). The K+ gates then close.
4. REFRACTORY PERIOD – consists of two
processes:
a. excess K+ in ECF diffuses away to re-establish
-65mV resting potential.
b. Na+ gates are unable to open for a certain period of
time (this disallows a backward nerve signal
whenever it is initiated at the axon hillock).
*once depolarization is complete, and the refractory
period passes, that particular section of the axon is
able to ‘fire’ again – this is due to the fact that, even
though ions changed places and did not return, only
a small percentage of the TOTAL Na+ and K+
swapped locations. A section of an axon may fire
multiple times before it requires a Recovery Period
(Ion Redistribution period), where both gates shut
down so that the Na+/K+ pump can get the ions back
to where they originally came from.
As a class, let’s re-draw an Action potential curve…
All-or-None Depolarization
- Action potentials are all of equal strength (ie. if a
stimulus is received, it either reaches threshold, and
therefore +40mV (Na+ equilbrium) or it does not
and resting potential is maintained).
- So, how does a stronger stimulus affect nerve firing?
- A stronger stimulus simply produces more APs per unit
time than does a weaker stimulus (that attains threshold).
- Thus, the refractory period for a neuron conducting a
stronger signal (more APs) is shorter than that of a
neuron conducting a weaker signal (less APs).
- This is important during stressful situations as,
eventually, neurons need a recovery period (pump
working feverishly), yet the signal must persist – this is
where hormones come into play to maintain a signal.
Propagation of an Action Potential (Domino Effect)
• An AP (depolarization/repolarization) is a localized event that
tends to originate at the axon hillock.
• APs need to ‘travel’ along an axon to carry the signal – the
‘traveling’ is actually due to simple diffusion of Na+ within the
axoplasm.
• Once Na+ floods the axon (depolarization), the ions diffuse in
either direction in the axon (from higher to lower conc.).
• Na+ that diffuses forward in the axon allows the axoplasm in this
‘non-stimulated region’ to reach threshold (cations raise voltage
to –40mV), which triggers the Na+ gates in this ‘new’ axon
region to open, so that more Na+ may flood across the
axomembrane.
• The Na+ that flows backward has no effect since that region of
the axon is experiencing the refractory period where Na+ gates
can not open for a period of time – thus, APs cannot travel
backward.
Myelin
• Myelin is a lipid that serves as a neuron insulator by wrapping
around axons (and dendrites in sensory neurons).
• It is composed of Schwann Cells (aka oligodendrocytes or
neurolemmocytes).
• Myelin serves to increase the speed of an AP’s (nerve impulse’s)
propagation by simply acting as a physical barrier to ion flow
(both Na+ and K+).
• Axons are not continuously covered by myelin; the myelin
sheath is interrupted at regular intervals by nodes (‘naked’ or
‘bare’ axon regions) called Nodes of Ranvier.
• The specific Na+ and K+ gates congregate at the nodes in
myelinated neurons – therefore, depolarization and
repolarization may only occur at the nodes.
• Thus, APs propagate (‘jump’) from node to node (known as
Saltatory Conduction).
• Non-myelinated neurons’ APs travel much more slowly…
Communication between Neurons and Other Cells
•
•
When an AP arrives at the many synaptic endings
(axon bulbs), the ‘signal’ must somehow be
passed on to another cell for its desired effect to
occur (remember: synaptic endings DO NOT
touch target cells).
There are three possible target cells:
i. Another Neuron – the connection is called a synapse;
ii. Muscle Cell – the connection is called a
neuromuscular junction (synapse);
iii. Gland or Organ Cell – the connection is called a
neuroglandular junction (synapse).
• Major focus will be on the synapses between
neurons, which conduct signals from an axon’s
synaptic endings to the dendrites (or cell bodies, in
some cases) of the next neuron in a signal pathway.
• The transmitting cell (the cell trying to ‘pass on’ the
AP) is called the presynaptic cell and it possesses its
own membrane, the presynaptic membrane.
• The receiving cell (the cell destined to ‘receive’ the
AP) is called the postsynaptic cell and it possesses
its own membrane, the postsynaptic membrane.
• The space between the two neurons is known as the
synaptic cleft (really, it’s just ECF with a max.
width of 0.2 micrometers).
• There exist two types of synapses: Electrical and
Chemical  we will focus primarily on the chem.
• Electrical Synapses: allows APs to spread directly
from pre- to postsynaptic cells. The cells are
connected by gap junctions (recall SA node
signaling in heart for atrial contraction), which
allow for direct ion transfer between neurons
(much faster, but more energy/coordination to
control); chemical synapses FAR outnumber
electrical synapses in the body.
Gap Junctions
Chemical Synapses (aka ‘Synapses’) see fig. 17.5 p. 326
• The synaptic endings of presynaptic cells contain
vesicles that are full of tiny chemical ‘messengers’
known as neurotransmitters; each vesicle is
attached to the presynaptic membrane by a special,
thread-like contractile protein (fiber) (primarily
composed of actin – a microfilament).
• The postsynaptic membranes possess multiple,
specific protein receptors for these neurotransmitters to bind to; a different type of neurotransmitter will bind to a different receptor and will
produce a different resulting signal.
The Transmission Process:
1. When an AP arrives at a synaptic ending, Na+ floods into
the axon bulb, which serves to signal different channels to
open (Ca2+ channels), which are only located in the
synaptic endings. Ca2+, which predominantly exist within
the synaptic cleft, then flood the bulb (of course, K+
leaves to repolarize).
2. Ca2+ bind to the contractile proteins and cause them to
CONTRACT and shorten, thus pulling the vesicles to the
presynaptic membrane.
3. Exocytosis occurs at the mb to release the neurotransmitter
into the synaptic cleft (many mitochondria exist within the
axon bulb in order to promote this active process). Once
enough vesicles have released their neurotransmitters, the
ATP from the mitochondria helps to actively transport the
Ca2+ ions back out of the bulb into the synaptic cleft.
4. Chemical neurotransmitters simply diffuse across the
synaptic cleft into the vicinity of the postsynaptic membrane
(cell).
5. The neurotransmitters bind with their specific, respective
protein receptors that are immersed within the postsynaptic
membrane.
6. One of six outcomes may occur depending on the type of
postsynaptic cell and the type of neurotransmitter/receptor
combo at work. Recall the three types of postsynaptic cells:
another neuron, a muscle cell, or a gland/organ cell. The
two different neurotransmitters that we talk about are
norepinephrine (excitatory) (aka ‘noradrenalin’) and
acetylcholine (inhibitory)…thus, they promote contrasting
effects upon their target postsynaptic cells:
Type of
Cell
Another
Neuron
Muscle Cell Gland/Organ
Cell
Neurotransmitter
Generates AP Causes
in postsynaptic muscle cells
to contract.
Norepinephrine neuron by
triggering Na+
gates to open.
Acetylcholine
Causes K+ gates (or
Cl- gates) to open;
causes a hyperpolarization of
postsynaptic cell;
AP not generated.
Causes
muscle cells
to relax.
Causes, for
example, a
gland to secrete
an enzyme or
hormone.
Causes, for
example, a gland
to stop secreting
an enzyme or
hormone.
Norepinephrine initiates an excitatory postsynaptic
potential (EPSP).
Acetylcholine initiates an inhibitory postsynaptic
potential (IPSP).
7. Receptors release the neurotransmitters back into
the synaptic cleft after their signaling function is
completed. To prevent perpetual stimulation or
inhibition, these ‘used’ neurotransmitters need to
be removed from the cleft. The following outlines
how this is done:
i. They are reabsorbed (endocytosis) by the
presynaptic cell’s synaptic ending (axon bulb).
ii. They simply diffuse away from the receptors.
iii. They are destroyed by enzymes that exist on the
postsynaptic membrane (the enzymes are activated
when the neurotransmitter is released back into the
cleft):
Monoamine Oxidase destroys norepinephrine;
Acetylcholinesterase destroys acetylcholine.
* Some drugs work to promote a continued existence
of neurotransmitters within the cleft so that their
excitatory/inhibitory effects occur over a lengthy
period of time (eg. Cocaine = excitatory; Heroin =
inhibitory).
Summation/Integration at Synapses
• A single neuron possesses numerous dendrites along with
the cell body, each of which synapse with thousands of
synaptic endings of other neurons in a relatively small
volume of space (if you recall, many neurons are bundled
into nerves).
• Because the cleft is a ‘sea’, of sorts, many different
neurotransmitters might be ‘floating’ around affecting many
synapses.
• Thus, a postsynaptic cell might be receiving a differing
combination of excitatory and inhibitory neurotransmitters
(eg. all of one type, or a mix of each), which possess the
ability to cause either depolarization (opening of Na+ gates)
or hyperpolarization (opening of K+ gates).
• The cell body and axon hillock then sum up (integrate) the
ions received (Na+) and lost (K+) to ‘decide’ if threshold is
reached (see fig. 17.6 p. 327).
• If threshold is not reached, no AP is generated in the axon
hillock;
• If threshold is reached, an AP is generated and continues at
the same strength along the length of the axon to the
postsynaptic cell’s synaptic endings.
• Two types of summation:
– Temporal Summation: neurotransmitter of one type released
rapidly from one presynaptic nerve (bundle of neurons) so as
to trigger a particular summed response;
– Spatial Summation: several different synaptic endings
belonging to different presynaptic cells (nerves) stimulate a
postsynaptic cell at the same time and have an additive effect.