Activity 2: Nerve Action Potential

 Firing Level (Threshold Level)

In electrophysiology, the threshold potential is the critical level to which a
membrane potential must be depolarized to initiate an action potential. In
neuroscience, threshold potentials are necessary to regulate and
propagate signaling in both the central nervous system (CNS) and the
peripheral nervous system (PNS).
Most often, the threshold potential is a membrane potential value between
–50 and –55 mV, but can vary based upon several factors. A neuron's
resting membrane potential (–70 mV) can be altered to either increase or
decrease the likelihood of reaching the threshold via sodium and potassium
ions. An influx of sodium into the cell through open, voltage-gated sodium
channels can depolarize the membrane past the threshold and thus excite
it while an efflux of potassium or influx of chloride can hyperpolarize the cell
and thus inhibit the threshold from being reached.
The resting potential tells about what happens when a neuron is at rest. An
action potential occurs when a neuron sends information down an axon,
away from the cell body. Neuroscientists use other words, such as a
"spike" or an "impulse" for the action potential. The action potential is an
explosion of electrical activity that is created by a depolarizing current. This
means that some event (a stimulus) causes the resting potential to move
toward 0 mV. When the depolarization reaches about -55 mV a neuron will
fire an action potential. This is the threshold. If the neuron does not reach
this critical threshold level, then no action potential will fire. Also, when the
threshold level is reached, an action potential of a fixed sized will always
fire...for any given neuron, the size of the action potential is always the
same. There are no big or small action potentials in one nerve cell - all
action potentials are the same size. Therefore, the neuron either does not
reach the threshold or a full action potential is fired - this is the "ALL OR
NONE" principle.

Physiological function and characteristics

The threshold value controls whether or not the incoming stimuli are
sufficient to generate an action potential. It relies on a balance of incoming
inhibitory and excitatory stimuli. The potentials generated by the stimuli are
additive, and they may reach threshold depending on their frequency and
amplitude. Normal functioning of the central nervous system entails a
summation of synaptic inputs made largely onto a neuron's dendritic tree.
These local graded potentials, which are primarily associated with external
stimuli, reach the axonal initial segment and build until they manage to
reach the threshold value. The larger the stimulus, the greater the
depolarization, or attempt to reach threshold. The task of depolarization
requires several key steps that rely on anatomical factors of the cell. The
ion conductances involved depend on the membrane potential and also the
time after the membrane potential changes.
Resting membrane potential
The phospholipid bilayer of the cell membrane is, in itself, highly
impermeable to ions. The complete structure of the cell membrane includes
many proteins that are embedded in or completely cross the lipid bilayer.
Some of those proteins allow for the highly specific passage of ions, ion
channels. Leak potassium channels allow potassium to flow through the
membrane in response to the disparity in concentrations of potassium
inside (high concentration) and outside the cell (low). The loss of positive(+)
charges of the potassium(K+) ions from the inside of the cell results in a
negative potential there compared to the extracellular surface of the
membrane.[7] A much smaller "leak" of sodium(Na+) into the cell results in
the actual resting potential, about –70 mV, being less negative than the
calculated potential for K+ alone, the equilibrium potential, about –90 mV.
[7] The sodium-potassium ATPase is an active transporter within the
membrane that pumps potassium (2 ions) back into the cell and sodium (3
ions) out of the cell, maintaining the concentrations of both ions as well as
preserving the voltage polarization.

Depolarization
However, once a stimulus activates the voltage-gated sodium channels to
open, positive sodium ions flood into the cell and the voltage increases.
This process can also be initiated by ligand or neurotransmitter binding to a
ligand-gated channel. More sodium is outside the cell relative to the inside,
and the positive charge within the cell propels the outflow of potassium ions
through delayed-rectifier voltage-gated potassium channels. Since the
potassium channels within the cell membrane are delayed, any further
entrance of sodium activates more and more voltage-gated sodium
channels. Depolarization above threshold results in an increase in the
conductance of Na sufficient for inward sodium movement to swamp
outward potassium movement immediately.[3] If the influx of sodium ions
fails to reach threshold, then sodium conductance does not increase a
sufficient amount to override the resting potassium conductance. In that
case, subthreshold membrane potential oscillations are observed in some
type of neurons. If successful, the sudden influx of positive charge
depolarizes the membrane, and potassium is delayed in re-establishing, or
hyperpolarizing, the cell. Sodium influx depolarizes the cell in attempt to
establish its own equilibrium potential (about +52 mV) to make the inside of
the cell more positive relative to the outside.

Variations
The value of threshold can vary according to numerous factors. Changes in
the ion conductances of sodium or potassium can lead to either a raised or
lowered value of threshold. Additionally, the diameter of the axon, density
of voltage activated sodium channels, and properties of sodium channels
within the axon all affect the threshold value.[8] Typically in the axon or
dendrite, there are small depolarizing or hyperpolarizing signals resulting
from a prior stimulus. The passive spread of these signals depend on the
passive electrical properties of the cell. The signals can only continue along
the neuron to cause an action potential further down if they are strong
enough to make it past the cell's membrane resistance and capacitance.
For example, a neuron with a large diameter has more ionic channels in its
membrane than a smaller cell, resulting in a lower resistance to the flow of
ionic current. The current spreads quicker in a cell with less resistance, and
is more likely to reach the threshold at other portions of the neuron.[3]
The threshold potential has also been shown experimentally to adapt to
slow changes in input characteristics by regulating sodium channel density
as well as inactivating these sodium channels overall. Hyperpolarization by
the delayed-rectifier potassium channels causes a relative refractory period
that makes it much more difficult to reach threshold. The delayed-rectifier
potassium channels are responsible for the late outward phase of the
action potential, where they open at a different voltage stimulus compared
to the quickly activated sodium channels. They rectify, or repair, the
balance of ions across the membrane by opening and letting potassium
flow down its concentration gradient from inside to outside the cell. They
close slowly as well, resulting in an outward flow of positive charge that
exceeds the balance necessary. It results in excess negativity in the cell,
requiring an extremely large stimulus and resulting depolarization to cause
a response.

 All or None Principle

The all-or-none law is a principle that states that the strength of a response
of a nerve cell or muscle fiber is not dependent upon the strength of the
stimulus. If a stimulus is above a certain threshold, a nerve or muscle fiber
will fire. Essentially, there will either be a full response or there will be no
response at all for an individual neuron or muscle fiber.

How Does the All-or-None Law Work?

If a stimulus is strong enough, an action potential occurs and a neuron
sends information down an axon away from the cell body and toward the
synapse. Changes in cell polarization result in the signal being propagated
down the length of the axon.
The action potential is always a full response. There is no such thing as a
"strong" or "weak" action potential. Instead, it is an all-or-nothing process.
This minimizes the possibility that information will be lost along the way.
This process is similar to the action of pressing the trigger of a gun. A very
slight pressure on the trigger will not be sufficient and the gun will not fire.
When adequate pressure is applied to the trigger, however, it will fire.
The speed and force of the bullet are not affected by how hard you pull the
trigger. The gun either fires or it does not. In this analogy, the stimulus
represents the force applied to the trigger while the firing of the gun
represents the action potential.
Determining Stimulus Strength
The body still needs to determine the strength or intensity of a stimulus. It's
important to know, for example, how hot a cup of coffee is as you take an
initial sip, or to determine how firmly someone is shaking your hand.
In order to gauge stimulus intensity, the nervous system relies on the rate
at which a neuron fires and how many neurons fire at any given time. A
neuron firing at a faster rate indicates a stronger intensity stimulus.
Numerous neurons firing simultaneously or in rapid succession would also
indicate a stronger stimulus.
If you take a sip of your coffee and it is very hot, the sensory neurons in
your mouth will respond at a rapid rate. A very firm handshake from a co-
worker might result in both rapid neural firing as well as a response from
many sensory neurons in your hand. In both cases, the rate and number of
neurons firing provide valuable information about the intensity of the
original stimulus.

Discovery of the All-or-None Law

The all-or-none law was first described in 1871 by physiologist Henry
Pickering Bowditch. In his descriptions of the contraction of the heart
muscle, he explained, "An induction shock produces a contraction or fails to
do so according to its strength; if it does so at all, it produces the greatest
contraction that can be produced by any strength of stimulus in the
condition of the muscle at the time."
While the all-or-none law was initially applied to the muscles of the heart, it
was later found that neurons and other muscles also respond to stimuli
according to this principle.

Reference:
https://www.verywellmind.com/what-is-the-all-or-none-law-
2794808#:~:text=The%20all%2Dor%2Dnone%20law,or%20muscle
%20fiber%20will%20fire.
https://en.wikipedia.org/wiki/Threshold_potential
https://faculty.washington.edu/chudler/ap.html#:~:text=When%20the
%20depolarization%20reaches%20about,no%20action%20potential
%20will%20fire.