2. IntroductionIntroduction
Neurons are electrically excitable.
They communicate each other using two types of
electrical signals:
1. Graded potentials
- used for short distance communication
2. Action potentials
- used for long distance communication
The production of graded and action potential is
depends on basic features of plasma membrane of
excitable cells:
1. Existence of resting membrane potentials
2. Presence of specific ion channels
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3. Types of Ion ChannelsTypes of Ion Channels
Leakage (nongated) channels are always open
nerve cells have more K+ than Na+ leakage channels
as a result, membrane permeability to K+ is higher
explains resting membrane potential of -70mV in nerve
tissue
Ligand-gated channels open and close in
response to a stimulus
results in neuron excitability
Voltage-gated channels respond to a direct
change in the membrane potential.
Mechanically gated ion channels respond to
mechanical vibration or pressure.
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4. Resting Membrane PotentialResting Membrane Potential
RMP is the cell membrane of a non-
conduction or in the resting state.
The difference in charges on the two sides of
the resting membrane is called the RMP.
This potentials is about – 70 milivolts (mV)
Negative ions along inside of cell membrane
& positive ions along outside
potential energy difference at rest is -70 mV
cell is “polarized”
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5. Resting Membrane PotentialResting Membrane Potential
Resting potential exists because
concentration of ions different inside & outside
extracellular fluid rich in Na+ and Cl
cytosol full of K+, organic phosphate &
amino acids
membrane permeability differs for Na+ and K+
50-100 greater permeability for K+
inward flow of Na+ can’t keep up with
outward flow of K+
Na+/K+ pump removes Na+ as fast as it
leaks in
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6. Graded PotentialsGraded Potentials
Small deviations from resting potential of
-70mV
hyperpolarization = membrane has become more
negative
depolarization = membrane has become more
positive
The signals are graded, meaning they vary in
amplitude (size), depending on the strength
of the stimulus and localized.
Graded potentials occur most often in the
dendrites and cell body of a neuron.
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7. Generation of Action PotentialsGeneration of Action Potentials
An action potential (AP) or impulse is a sequence of
rapidly occurring events that decrease and eventually
reverse the membrane potential (depolarization) and
then restore it to the resting state (repolarization).
During an action potential, voltage-gated Na+
and
K+
channels open in sequence
According to the all-or-none principle, if a stimulus
reaches threshold, the action potential is always
the same.
A stronger stimulus will not cause a larger
impulse.
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8. 8
Conduction of nerve impulsesConduction of nerve impulses
Transmission of the impulses and action
potential due to movement of ion across the
nervous cell membrane.
In the resting state the nerve cell membrane
is polarised due to different concentration of
ion across the plasma membrane.
This condition is called resting membrane
potential.
9. 9
Resting membrane potential:
Sodium the main extracellular cation.
Potassium the main intracellular cation.
Conduction of nerve impulsesConduction of nerve impulses
10. 10
When stimulated, the permeability of the nerve cell
membrane to this ion change.
Sodium flood into the neuron from ECF causing
depolarisation, creating a nerve impuls @ action potential.
Depolarisation is very rapid.
Its passes from the point of stimulation in one direction
only.(away from the point towards the area of resting
membrane potential)
Conduction of nerve impulsesConduction of nerve impulses
12. 12
During this
process, potassium
floods out of the
neuron cell.
Depolarization
results because
inward diffusion of
sodium is much
greater than a
outward diffusion
of potassium
DEPOLARIZATIONDEPOLARIZATIONDEPOLARIZATIONDEPOLARIZATION
13. Depolarizing PhaseDepolarizing Phase
Chemical or mechanical stimulus caused a graded
potential to reachat least (-55mV or threshold)
Voltage-gated Na+ channels open
& Na+ rushes into cell
in resting membrane, inactivation gate of sodium
channel is open & activation gate is closed (Na+ can not
get in)
when threshold (-55mV) is reached, both open & Na+
enters
inactivation gate closes again in few ten-thousandths of
second
only a total of 20,000 Na+ actually enter the cell, but
they change the membrane potential considerably (up
to +30mV)
Positive feedback process
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14. 14
Voltage gated Na+ channels are closed.
Voltage gated channel K+ are open.
Sodium ion diffusion into the cell stops and K+
diffuse out of the cell, causing repolarisation.
Resting membrane potential is reestablish
after the voltage gated K+ channels closed.
REPOLARIZATIONREPOLARIZATIONREPOLARIZATIONREPOLARIZATION
15. When threshold potential of -55mV is reached,
voltage-gated K+ channels open
K+ channel opening is muchslower than Na+ channel
opening which caused depolarization
When K+ channels finally do open, the Na+ channels
have already closed (Na+ inflow stops)
K+ outflow returns membrane potential to -70mV
If enough K+ leaves the cell, it will reach a -90mV
membrane potential and enter the after-
hyperpolarizing phase
K+ channels close and the membrane potential
returns to the resting potential of -70mV
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17. 17
REFRACTORY PERIODREFRACTORY PERIODREFRACTORY PERIODREFRACTORY PERIOD
The period of time
after an action
potential begins
during which an
excitable cell
cannot generate an
action potential is
called refractory
period.
Second action
potential cannot
be initiated, even
with a very strong
stimulus.
18. Absolute refractory period
even very strong stimulus willnot begin another AP
inactivated Na+ channels must return to the resting
state before they can be reopened
large fibers have absolute refractory period of 0.4
msec and up to 1000 impulses per second are
possible
Relative refractory period
a suprathreshold stimulus will be able to start an AP
K+ channels are still open, but Na+ channels have
closed
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19. Continuous versus Saltatory ConductionContinuous versus Saltatory Conduction
Continuous conduction (unmyelinated fibers)
step-by-step depolarization of each portion of the
length of the axolemma
Saltatory conduction
depolarization only at nodes of Ranvier where there is a
high density of voltage-gated ion channels
current carried by ions flows through extracellular fluid
from node to node
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20. Propagation of an Action Potential in a neuron
after it arises at the trigger zone
Propagation of an Action Potential in a neuron
after it arises at the trigger zone
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21. Factors that affect speed of propagationFactors that affect speed of propagation
Amount of myelination
Axon diameter
Temperature
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Speed of impulse propagationSpeed of impulse propagation
• The propagation speed of a nerve
impulse is not related to stimulus
strength.
– larger, myelinated fibers conduct
impulses faster due to size & saltatory
conduction
22. Fiber typesFiber types
A fibers largest (5-20 microns & 130 m/sec)
myelinated somatic sensory & motor to skeletal muscle
Sensory neurons associated with touch, pressure, position
of joints, some thermal sensations.
Motor neurons conduct impulses to skeletal muscles.
B fibers medium (2-3 microns & 15 m/sec)
myelinated visceral sensory & autonomic preganglionic
sensory nerve impulse from viscera to brain and spinal
cord.
Also constitute all axons of autonomic motor neurons that
extend from the brain and spinal cord to ANS relay
stations called autonomic ganglia.
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23. – C fibers smallest (.5-1.5 microns & 2 m/sec)
unmyelinated sensory & autonomic motor
Conduct sensory impulses for pain, touch, pressure, heat
and cold from the skin and pain from viscera.
Autonomic motor fiber that extend from autonomic
ganglia to the heart, smooth muscle and glands are also C
fibers.
E.g. motor functions of B and C fibers are constricting and
dilating the pupils, increasing and decreasing heart rate,
and contracting and relaxing the urinary bladder.
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25. Definition
The site of communication between 2 neurons or
between neuron and effector cells (muscles or
glands).
The tips of some axon terminals swell into bulb
shaped structures called synaptic end bulbs.
Synaptic end bulbs contain many tiny membrane-
enclosed sacs called synaptic vesicles that store a
chemical called neurontransmitter.
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26. Neuron sending the signal is called the presynaptic
neuron.
Neuron receiving the message is called the
postsynaptic neuron.
2 types of synapse:
Electrical synapse
Action potential conducts directly between adjacent cells
through structures called gap junction.
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27. Gap Junctions
Connect neighboring cells via
tiny fluid-filled tunnels called
connexons
Contain membrane proteins
called connexins
Plasma membranes of gap
junctions are separated by a
very narrow intercellular
gap (space)
Communication of cells
within a tissue
Ions, nutrients, waste,
chemical and electrical
signals travel through the
connexons from one cell
to another
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28. Chemical synapse
Presynaptic and postsynaptic neuron
separated by synaptic cleft.
axodendritic -- from axon to dendrite
axosomatic -- from axon to cell body
axoaxonic -- from axon to axon
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29. NeurotransmittersNeurotransmitters
Both excitatory and inhibitory neurotransmitters are
present in the CNS and PNS; the same
neurotransmitter may be excitatory in some locations
and inhibitory in others.
Important neurotransmitters include acetylcholine,
glutamate, aspartate, gamma aminobutyric acid,
glycine, norepinephrine, epinephrine, and dopamine.
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30. Neurotransmitter EffectsNeurotransmitter Effects
Neurotransmitter effects can be modified
synthesis can be stimulated or inhibited
release can be blocked or enhanced
removal can be stimulated or blocked
receptor site can be blocked or activated
Agonist
anything that enhances a transmitters effects
Antagonist
anything that blocks the action of a neurotransmitter
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31. Small-Molecule NeurotransmittersSmall-Molecule Neurotransmitters
Acetylcholine (ACh)
released by many PNS neurons & some CNS
excitatory on NMJ but inhibitory at others
inactivated by acetylcholinesterase
Amino Acids
glutamate released by nearly all excitatory neurons
in the brain ---- inactivated by glutamate specific
transporters
GABA is inhibitory neurotransmitter for 1/3 of all
brain synapses (Valium is a GABA agonist --
enhancing its inhibitory effect)
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32. NeurontransmitterNeurontransmitter
1. Acetylcholine
Released by many PNS neurons and by some CNS
neuron.
Ach is an excitatory NT at some synapses, such as NMJ,
where its binding to ionotropic receptors and opens
cation channels.
Also an inhibitory NT at other synapse, where its bind
to metabotropic receptors that open potassium channel.
For example ACh slows rate heart rate at inhibitory
synapses made by parasympathetic neuron of the Vagus
nerve.
Inactivates Ach by enzyme acetylcholinestrase.
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34. Excitatory and Inhibitory TransmissionExcitatory and Inhibitory Transmission
In excitatory transmission, the
neurontransmitter-receptor reaction on the
postsynaptic membrane depolarises the
membrane and initiates Action Potential.
This is excitation or stimulation.
Acetylcholine is typically an excitatory
neurontransmitter.
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35. For inhibitory transmission, reaction between
the neurontransmitter and the receptor opens
potassium channel in the membrane so that
potassium diffuse out of the cells, but no effect
on the sodium channels.
This action makes the inside of the membrane
even more negative than its resting condition.
Its hyperpolarizes the membrane and makes it
more difficult to generate an Action Potential.
This is inhibitory action.
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36. 36
SIGNAL TRANSMISSION AT SYNAPSESSIGNAL TRANSMISSION AT SYNAPSES
Although the plasma membrane of presynaptic and
postsynaptic neuron in a chemical synapse are close, they
do not touch.
The synaptic cleft, a space of 20-50 nm that is filled with
interstitial fluid, separated the two neurons.
The presynaptic neuron converts an electrical signal
(nerve impuls) into a chemical signal (release
neurontransmitter).
The postsynaptic neuron receives the chemical signal and
generate an electrical signal (postsynatic potential).
37. Chemical SynapsesChemical Synapses
Action potential reaches end bulb and
voltage-gated Ca+ 2 channels open
Ca+2 flows inward triggering release of
neurotransmitter
Neurotransmitter crosses synaptic cleft &
binding to ligand-gated receptors
the more neurotransmitter released the greater
the change in potential of the postsynaptic cell
Synaptic delay is 0.5 msec
One-way information transfer
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38. 38
A typical chemical synapse transmits a signal as
follows:
1. A nerve impulse arrives at a synaptic end bulb of a
presynaptic axon.
2. The depolarizing phase of the nerve impulse opens
voltage gated Ca2+ channels, which are present in the
membrane of synaptic end bulbs.
3. Increase [Ca2+] inside the presynatic neuron is the
triggers exocytosis of some of the synaptic vesicles. As
vesicles membrane merge with the plasma membrane,
neorontransmitter molecules released into the
synaptic cleft.
SIGNAL TRANSMISSION AT SYNAPSESSIGNAL TRANSMISSION AT SYNAPSES
39. 39
4. The neurontrasmitter molecule diffuse across
the synaptic cleft and bind to
neurontransmitter receptor in the
postsynaptic neuron plasma membrane.
5. Binding of neurontransmitter molecules to
their receptor on ligand-gated channels opens
the channels and allow particular ions to flow
across the membrane.
SIGNAL TRANSMISSION AT SYNAPSESSIGNAL TRANSMISSION AT SYNAPSES
40. 40
SIGNAL TRANSMISSION AT SYNAPSESSIGNAL TRANSMISSION AT SYNAPSES
6. As ions flow through the opened channels,
the voltage across the membrane changes.
This change in membrane voltage is a
postsynaptic potential.
7. When a depolarizing postsynaptic potential
reaches threshold, it triggers one ore more
nerve impulse.
41. Neuromuscular Junction (NMJ)Neuromuscular Junction (NMJ)
Synapse between somatic motor neuron and
skeletal muscles fiber.
Structures of the presynaptic neuron same
with other neurons.
NT released in the synaptic cleft – Ach.
The region of the sarcolemma opposite to the
synaptic end bulbs are called motor end plate.
Within the motor end plate, there is many ACh
receptors.
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42. The Neuromuscular Junction
Motor neurons have a threadlike axon that extends from the brain or
spinal cord to a group of muscle fibers
Neuromuscular junction (NMJ)
Action potentials arise at the interface of the motor neuron and muscle
fiber
Synapse
Where communication occurs between a somatic motor neuron and a
muscle fiber
Synaptic cleft
Gap that separates the two cells
Neurotransmitter
Chemical released by the initial cell communicating with the second
cell
Synaptic vesicles
Sacs suspended within the synaptic end bulb containing molecules of
the neurotransmitter acetylcholine (Ach)
Motor end plate
The region of the muscle cell membrane opposite the synaptic end
bulbs
Contain acetylcholine receptors
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43. Neuromuscular Junction (NMJ)
A nerve impulses elicits a muscles action
potential in the following way:
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Release of Ach – arrival of impulses at the SEB causes many
synaptic vesicles undergo exocytosis. ACh liberate into
synaptic cleft and diffuse between motor neuron and
motor end plate.
Activation of Ach receptors – Binding of two molecules of Ach to the
receptors On the MEP open an ion channels in the Ach receptor.
Once the channel is open small cations most importantly Na+ can flow
across the membrane
44. Neuromuscular Junction (NMJ)
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Production of muscle action potential – the inflow of Na+ makes the inside
of the muscle fiber more positively charged. This change in the membrane
potential triggers a muscle action potential. The muscles AP that propagates
along the sarcolemma into T tubul system. This causes the sarcoplasmic
reticulum to release its stored Ca2+ into the sarcoplasm and the muscles
Fiber suddenly contracts.
Termination of Ach activity – Ach rapidly broken down by enzyme
Acetylcholinestrase. Ach break down into acetyl and choline, where
This product cant activate the Ach receptor.
45. Myasthenia GravisMyasthenia Gravis
Neuromuscular disease leading to fluctuating
muscle weakness.
Autoimmune disease, caused by antibodies in
the circulation, block the Ach receptor at the
postsynaptic neuromuscular junction.
Inhibit the stimulating effect of Ach.
Muscles become progressively weaker during
periods of activity and improve after periods
of rest.
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46. Myasthenia GravisMyasthenia Gravis
In most cases, the first
noticeable symptom is
weakness of the eye
muscles.
In others, difficulty in
swallowing and slurred
speech may be the first
signs.
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