Unit-1 Part-2

1.6 Propagation of the Action Potential/Impulse along the Nerve Fibre:

We had learned initially that nerve cells exhibit excitability and conductibility.
Conductibility is the capacity to conduct the electrical impulse along its
pathway. The way the conduction of the action potential occurs along the nerve fiber
depends on whether it’s myelinated or unmyelinated. Note: All muscle cells are un
myelinated, there is no insulation in muscle cells. Nerve cells could be either.
Conduction along an Unmyelinated Nerve Fibre (Continuous Conduction)
Initially, a threshold stimulus creates an action potential. As the nerve fiber
depolarizes, it triggers an increase in permeability of the ligand-gated sodium ion
channels that causes sodium channels to open and sodium ions go into the nerve
cell and reverse polarity because positively charged ions are flowing in. This action
potential is going to be conducted along the length of the fiber by cause the next
adjacent space to open voltage-gated sodium ion channels to open.
So as we go from left to right, sodiums are entering the cell due to these voltage-
gated sodium ion channels opening up and meanwhile, to the left of it, the
potassiums are going out. As the potassium ions go out, it repolarizes. This idea of
sodium coming in and potassium going out, is going to repeat constantly so it
appears to keep moving the electricity through the fiber.
Analogy: When you cause a ripple to move across the surface of the water, the wave
is moving along and each ripple is like sodium ions coming in and potassium ions
coming out.
In the picture below we see an impulse is transmitted as a wave of depolarization
that travels down the axon. At the region of depolarization, Na+ ions diffuse into the
cell. As the impulse passes, potassium ions flow outward until the resting potential
is restored. Then, what is not shown is the working of the Na+/K+ ATP pump that
pumps the sodium back out of the axon so that the resting conditions are
reestablished.
Propagation along a Myelinated Nerve Fiber (Saltatory Conduction)
In myelinated nerve fibers, the depolarized Node of Ranvier triggers an increase in
the permeability of the sodium ion channels (and thus depolarization) in the adjacent
Node of Ranvier.

Above we see a myelinated neuron. If the myelinated cells are wrapped around
interneurons, they are oligodendrocytes. If they’re wrapped around neurons in the
PNS they’re called Schwaan cells. In either case there are these gaps called Nodes of
Ranvier. The only place these potassium or sodium ions can enter or leave are from
these spaces that are unmyelinated. Sodiums come in and potassiums going out
just like a an unmymelinated nerve fiber, except this signal seems to jump from one
node to the next. This is called saltatory conduction. It has nothing to do with salt
but it comes from the latin word saltaire which means to jump or leap.
Due to this skipping, saltatory conduction is up to 50 times faster than conduction
through the fastest unmyelinated axons because they don’t have to travel
throughout every single space before moving to the next. So in essence, the action
potential is generated only at the nodes. The cell membranes below the myelin
sheaths hardly have any sodium channels and are therefore not excitable
anyway. Since the ionic currents are restricted to the nodes of Ranvier in the
myelinated axons, this minimizes disturbances in the Na+/K+ concentration
gradients which reduces the energy costs of the Na+/K+-ATP pump that have to
restore ionic balance.

Equivalent Circuit of an AXON:

  ri=The electrical equivalent of a segment of Axoplasm or intracellular fluid
 The electrical equivalent of a segment of membrane consists of three
components:
 Cm=capacity representing the insulating charge storing aspect of membrane
 rm= resistance representing the limited ability to ions to penetrate through
membrane
 Es= a battery of voltage represents the steady state potential
 ro= The electrical equivalent of extracellular fluid which can be neglected.

Voltage clamp technique

The action potential arises from coordinated activation of two conductances i,e
i) Sodium conductance that activates and drives rapidly rising phase of action
potential
ii) Potassium conductance that activates more slowly and contributes to falling
phase of action potential and undershoot

To learn more about these conductance’s :

One difficulty in studying the behaviour of the conductance is that they are changing
over time, rising and falling as the action potential proceeds. They also change with
voltage. Analyses could be made If one of these elements either time or voltage could
be controlled. Voltage clamp technique just does that it controls or clamps voltage
according to the investigator chooses to study either Na+ or K+ conductance
variation with time.
First the axon under study is placed in a dish containing saline solution.
The membrane voltage Vm is measured by an amplifier using an internal recording
electrode inserted into the axon and external reference electrode placed in the saline
bath. The command voltage Vc is the desired membrane voltage set by the
investigator, the difference between Vm and Vc is determined by the comparator. If
Vm is not equal to Vc this comparator generates a difference signal.
This difference signal is used by the voltage clamp amplifier to generate a current
that is injected into the axon via the current passing electrode in order to make Vm
equal to Vc. This feedback circuit keeps Vm as close to Vc as possible
instantaneously. Finally the injected current is measured and recorded.
Let’s try for simple example:
If Vm = Vc (i,e when Vc is set to -65mV by the investigator)
No currents are generated and injected into the axon as Vm =Vc
Now what happens when Vm = -65mV (which is steady ) and Vc = 0mV (as set by
investigator)
Now the voltage clamp amplifier injects current to push the membrane voltage to
0mV

Now different types of membrane channels open and close such that there is an
initial surge capacitive current followed by inward (due to Na+ conductance =INa due to
depolarisation )and outward currents(due to K+ conductance Ik due to repolarisation)
How do we know it is sodium inward and Potassium outward currents. Specific
blocking agents are used to block ion channels like TTX tetrodotoxin blocks sodium
channels and TEA tetraethyl ammonium blocks Potassium channels.
So by this we can conclude initial inward current during depolarisation is due to
sodium ions and delayed outward current is due to potassium ions during
repolarisation.
-----------------------------------------XXX--------------------------------
Synapse:
Synapse is the functional connection between two neurons. Therefore, it is the
junctional region where one neurone ends and the other begins. Between the pre-
synaptic and postsynaptic membranes a cleft of several nanometres is present.
The transfer of information across a synaptic junction is called synaptic
transmission. These transmissions are brought about either by chemical or by
electrical or by both processes.

Types of synapses
There are two types of synapses:
 electrical synapses
 chemical synapses

Electrical synapses
Electrical synapses are a direct electrical coupling between two cells
mediated by gap junctions, which are pores (as shown in the electron micrograph)
constructed of connexin proteins essentially result in the passing of a graded
potential (may be depolarizing or hyperpolarizing) between two cells very
rapid (no synaptic delay) passive process --> signal can degrade with distance--> may
not produce a large enough depolarization to initiate an action potential in the
postsynaptic cell bidirectional i.e., "post"synaptic cell can actually send messages to
the "pre"synaptic cell
Chemical synapses:
Chemical synapses are slow, active (require ligand-gated channels) pseudo-
unidirectional, compared to electrical synapses the probability that a presynaptic
action potential will produce a postsynaptic action potential is termed the SAFETY
FACTOR(a concept similar to security that will be discussed under neurotransmitter)
neither electrical nor chemical synapses are perfectly secure many central synapses
fail more than 50% of the time the neuromuscular junction may be the most secure
synapse; in healthy people, the safety factor of that synapse is > 50%
Main Difference – EPSP vs IPSP
Graded potentials and action potentials are two types of electric potentials that occur
in the nervous system. The graded potentials arise by the action of ligand-gated ion
channel proteins. The action potentials arise by the voltage-gated sodium and
potassium channels. The graded potentials differ based on the location and function.
The different types of graded potentials are postsynaptic potentials, pacemaker
potentials, receptor potentials, end-plate potentials, and slow-wave potentials. The
two types of postsynaptic potentials are EPSP and IPSP. EPSP stands for the
Excitatory Postsynaptic Potential and IPSP stands for the Inhibitory Postsynaptic
Potential. EPSP is a temporary depolarization that is caused by the flow of positively-
charged ions into the postsynaptic cell while IPSP is a hyperpolarization caused by
the flow of negatively-charged ions into the postsynaptic cell. The main difference
between EPSP and IPSP is that EPSP facilitates the firing of an action potential on
the postsynaptic membrane whereas IPSP lowers the firing of the action potential.
Excitatory Postsynaptic Potential (EPSP)
An Excitatory Postsynaptic Potential (ESPS) refers to an electric charge in the
postsynaptic membrane, which makes the postsynaptic membrane to generate an
action potential. The EPSP is caused by the binding of the excitatory
neurotransmitters, which are released from the presynaptic membrane. The
excitatory neurotransmitters are released from the vesicles of the presynaptic nerve.
Several EPSPs generating an action potential is shown in figure 1.

Difference Between EPSP and IPSP

Figure 1: EPSPs Generating an Action Potential

The main excitatory neurotransmitter is glutamate. The acetylcholine serves as the

excitatory neurotransmitter at the neuromuscular junction. These excitatory
neurotransmitters bind to the receptors and open the ligand-gated channels. This
causes the flow of the positively-charged sodium ions into the postsynaptic cell. The
depolarization of the postsynaptic membrane generates an action potential on the
postsynaptic nerve.

Inhibitory Postsynaptic Potential (IPSP)

The Inhibitory Postsynaptic Potential (IPSP) refers to an electric charge on the
postsynaptic membrane, which makes the postsynaptic membrane less likely to
generate an action potential. The IPSP is caused by the flow of negatively-charged
chloride ions into the postsynaptic neuron. The inhibitory neurons secret the
inhibitory neurotransmitters to the synapse. The most common inhibitory
neurotransmitters are glycine and GABA.

Figure 2: Formation of an IPSP

The formation of an IPSP is described in the flowchart in figure 2.

The binding of the inhibitory neurotransmitters to the receptors of the postsynaptic
membrane causes the opening of the ligand-gated chloride ion channels. This results
in a hyperpolarization of the postsynaptic membrane. The hyperpolarization makes
the postsynaptic membrane less likely to generate an action potential.

Similarities Between EPSP and IPSP

Both EPSP and IPSP are two types of postsynaptic potentials.

Both EPSP and IPSP occur on the postsynaptic cell membrane.
Both EPSP and IPSP are mediated by ligand-gated ion channels, which are
opened by the binding of neurotransmitters.

Difference between EPSP and IPSP

EPSP: An EPSP is an electrical charge on the postsynaptic membrane, which is

caused by the binding of excitatory neurotransmitters and makes the postsynaptic
membrane generate an action potential.
IPSP: An IPSP is an electric charge on the postsynaptic membrane, which is caused
by the binding of inhibitory neurotransmitters and makes the postsynaptic
membrane less likely to generate an action potential.
EPSP: EPSP stands for Excitatory Postsynaptic Potential.
IPSP: IPSP stands for Inhibitory Postsynaptic Potential.

Cause for PSP

EPSP: EPSP is caused by the flow of positively-charged ions.
IPSP: IPSP is caused by the flow of negatively-charged ions.

Type of Polarization
EPSP: EPSP is a depolarization.
IPSP: IPSP is a hyperpolarization.
To the Threshold
EPSP: EPSP brings the postsynaptic membrane towards the threshold.
IPSP: IPSP takes the postsynaptic membrane away from the threshold.

Excitation
EPSP: EPSP makes the postsynaptic membrane more excited.
IPSP: IPSP makes the postsynaptic membrane less excited.
Firing of an Action Potential
EPSP: EPSP facilitates the firing of an action potential on the postsynaptic
membrane.
IPSP: IPSP lowers the firing of an action potential on the postsynaptic membrane.

Results
EPSP: EPSP is the result of the opening of the sodium channels.
IPSP: IPSP is the result of the opening of the potassium or chloride channels.
Types of Ligands
EPSP: EPSP is generated by the flow of glutamate or aspartate ions.
IPSP: IPSP is generated by the flow of glycine or GABA.

Conclusion
EPSP and IPSP are the two types of electric charges found on the membrane of the
postsynaptic nerve at the synapse. The EPSP is caused by the flow of positively-
charged ions into the postsynaptic nerve whereas; the IPSP is caused by the flow of
negatively-charged ions into the postsynaptic nerve. The EPSP facilitates the
generation of an action potential on the postsynaptic membrane whereas the IPSP
inhibit the generation of an action potential. The main difference between EPSP and
IPSP is the effect of each type of electric charges on the postsynaptic membrane.
Properties of Synapse:

1. One-way conduction (unidirectional conduction):

In chemical synapse, since neurotransmitter is present only in presynaptic region,
impulse gets conducted from pre- to postsynaptic region only and not vice versa.
2. Synaptic delay is for neurotransmitter to:
a. Get released from synaptic vesicles when action potential has reached presynaptic
region.
b. Pass through synaptic cleft.
c. Act on postsynaptic region to bring about production of action potential in
postsynaptic region.
For all the above events to be brought about, sometime is required. This is known as
synaptic delay, which is normally about 0.5 msec at every synapse.

3. Fatigability:
When synapses are continuously stimulated, after some time, due to exhaustion of
neurotransmitter at presynaptic terminals, impulses fail to get conducted. This
results in fatigue occurring at level of synapse. Fatigue is a temporary phenomenon.
If some rest is given to neurons, resting facilitates resynthesis of neurotransmitter
for further conduction of impulse across synapse.

4. Convergence and divergence:

Impulses from one pre-synaptic nerve fiber may end on postsynaptic region of large
number neurons and this is called as divergence. When nerve fibers of different
pre-synaptic neurons end on a common postsynaptic neuron, this is known as
convergence. In CNS, on an average about 10000 synapses are found on any one
neuron.

5. Summation:
Summation is the process of adding things up.When a stimulus of subthreshold
strength is applied, there will not be development of action potential in postsynaptic
region. But if many subthreshold stimuli are applied at pre-synaptic region, effects of
these stimuli can get added up and lead to action potential development in
postsynaptic region. This is known as summation.

There are two types of summation namely spatial and temporal. In temporal
summation, pre-synaptic neuron stimulated will be same, but many stimuli are
applied in rapid succession (timing of stimuli will be different, but place of
stimulation will be same). In spatial summation, presynaptic neurons stimulated
will be different but stimuli will be applied simultaneously (time of stimulation shall
be same, but places of stimulation will be different). This is possible because of the
property of convergence.
Spatial summation: Spatial summation is the effect of triggering an action potential
in a neuron from one or more presynaptic neurons[2]. This occurs when more than
one excitatory postsynaptic potential (EPSP) originates simultaneously and a
different part of the neurone. If all of the EPSPs are subthreshold then an action
potential will not be fired once they reach the neurone individually. However, if they
all stimulate the neurone simultaneously at the trigger zone, then the subthreshold
EPSP’s will sum up to create a suprathreshold that exceed the threshold voltage
which will then generate an action potential.
Another form of spatial summation is that which involve an inhibitory postsynaptic
potential (IPSP) which reaches the neurone at the same time as the multiple EPSPs
and the sum of the IPSP and EPSP’s (the summed potential) is subthreshold so no
action potential is generated as the IPSP has diminished the EPSPs. Spatial
summation in this example is known as postsynaptic inhibition.
Temporal summation
This happens when the summation of graded potentials originates from one
presynaptic neurone or in other words, the signals overlap reaching a postsynaptic
neurone. If a subthreshold EPSP reaches the neurone then no action potential will be
generated, however, if multiple subthreshold EPSPs reach the neurone trigger zone
close enough together in time then the two subthreshold EPSPs will sum up to cause
a suprathreshold EPSP and an action potential will be generated. This is an example
of postsynaptic integration.

6. Excitation or inhibition:The impulse conduction across a synapse may either

stimulate or inhibit activity of postsynaptic region. If there is stimulatory influence,
then there will be production of action potential in postsynaptic neuron and if it has
an inhibitory influence, then there is no action potential generation in postsynaptic
region.