2013 Pearson Education, Inc.

ANP 1105A&E
Anthony Krantis, PhD
akrantis@uottawa.ca

Cellular Physiology of Nerve & Muscle

2.2

Neurons

These slides contain material to be presented in lecture*.

The information from the lecture should be used in combination with the
relevant chapters of the recommended Text book(s).
Throughout this presentation, there are references to and use of figures
from the text book. In addition, specific animations/videos
are also referenced and can be used by the student for
study purposes, if they wish.
*Slides marked with a STAR will not be covered in the lecture but are
provided as additional learning material
Slides includes material (direct or modified) from 2013 Pearson Education, Inc. Human Anatomy & Physiology, Ninth Edition
together with material provided by Dr J Carnegie and other sources as referenced

The Nervous System

Master control
Human brain ~ 1 trillion cells
86-100bn neurons
~ 900bn glial cells
100trill synapses - electrical &
chemical

Central nervous system (CNS)

Brain and spinal cord
Integrative and control centers

Peripheral nervous system (PNS)

Cranial nerves and spinal nerves
Communication lines between the CNS
and the rest of the body

Sensory (afferent) division

Somatic and visceral sensory
nerve fibers
Conducts impulses from
receptors to the CNS

Somatic sensory fiber

Figure 11.2 Levels of

organization in the nervous
system.

Skin

Visceral sensory fiber

Stomach

Motor (efferent) division

Motor nerve fibers
Conducts impulses from the CNS
to effectors (muscles and glands)

Somatic nervous
system
Somatic motor
(voluntary)
Conducts impulses
from the CNS to
skeletal muscles
Skeletal
muscle

Autonomic nervous
system (ANS)
Visceral motor
(involuntary)
Conducts impulses
from the CNS to
cardiac muscles,
smooth muscles,
and glands

Motor fiber of somatic nervous system

Sympathetic division
Mobilizes body systems
during activity

( lecs Sept 30)

Sympathetic motor fiber of ANS
Structure
Function
Sensory (afferent)
division of PNS

Motor (efferent)
division of PNS

Parasympathetic motor fiber of ANS

Parasympathetic
division
Conserves energy
Promotes housekeeping functions
during rest

Heart

Bladder

Also Enteric Nervous System(ENS): Separate from CNS & ANS

Neurons
Highly specialized cells that
conduct electrical impulses
Extreme longevity (100 yrs)
Amitotic
High metabolic rate - requires
continuous supply of 02 and
glucose
All have cell body and one or
more processes

Neuron Cell Body (Perikaryon/Soma)

Biosynthetic centre of neuron
Synthesizes the essential chemistry
Most active and best developed
of any cell type
Spherical nucleus with nucleolus
Some contain pigments

PVN

Most CNS neuron bodies are

in Nuclei clusters of cell bodies

In the PNS- cell bodies

are in Ganglia

DRG

Sensory neurons

Dendrites
(receptive
regions)

STRUCTURE OF MOTOR NEURON

Cell body
(biosynthetic center
and receptive region)

Nucleus

Axon
Nucleolus
Chromatophilic
substance (rough
endoplasmic
reticulum)
Axon hillock

(impulsegenerating
and -conducting
region)

Impulse
direction

Schwann cells
Terminal branches

Figure 11.4a Motor neuron

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Myelin sheath gap

(node of Ranvier)
Axon
terminals
(secretory
region)

Dendrites
In motor neurons
100s of short, tapering, diffuse processes
Same organelles as in body
Receptive (input) region of the neuron
Convey incoming messages toward cell body as
graded potentials (short distance signals)
In many brain areas fine dendrites specialized
Collect information with dendritic spines
Appendages with bulbous or spiky ends

The Axon
One axon/cell arising from axon hillock
In some, axons short or absent
Usually represent most of length of cell
Some 1 metre long
Long axons called nerve fibers
Occasional branches (axon collaterals)
Branch profusely at end (terminus)
Can have 10,000 terminal branches
Distal endings = axon terminals or boutons
Many neurons don t have end boutons

Gut neurons

The Axon: Functional Characteristics

Generates nerve impulses
Transmits them along axolemma (cell
membrane) to axon terminal
- Neurotransmitters released from nerve
endings
- Either excite or inhibit neurons
Carries on many conversations with
different neurons at same time
Lacks rough ER and Golgi apparatus
Relies on cell body to renew proteins and
membranes
Efficient transport mechanisms
Quickly decay if cut or damaged eg Spinal
Injury

Additional Information
- Will not be in the exam

The cell body is lost if the axon

is severed close to the cell
body, but there is a chance
that the axon will regenerate,
even in the CNS
The postsynaptic, (& presynaptic),
neurons are also affected and
may degenerate

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Axonal Transport
Molecules and organelles moved along axons
by motor proteins and cytoskeletal elements
Movement is bi-directional
Retrograde
Examples: organelles to be degraded, signal
molecules, viruses, and bacterial toxins

Anterograde
Examples: mitochondria, cytoskeletal elements,
membrane components, enzymes

Myelin Sheath
Composed of myelin
Whitish, protein-lipoid substance
Segmented sheath around long or large-diam. axons
Called Myelinated fibers
Function
Protects and electrically insulates axon
Increases speed of nerve impulse transmission
Non-myelinated fibers conduct impulses more slowly

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Figure 11.5a Nerve fiber myelination in the PNS

Schwann
cell plasma
membrane
Schwann cell
cytoplasm
Axon

1 A Schwann cell envelops an axon.

Schwann cell
nucleus

2 The Schwann cell then rotates

around the axon, wrapping its
plasma membrane loosely around
it in successive layers.

Myelin
sheath

3 The Schwann cell cytoplasm is

forced from between the membranes.
The tight membrane wrappings
surrounding the axon form the myelin
sheath.

Schwann cell cytoplasm

Myelination of a nerve fiber (axon)

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Structural Classification of Neurons

Multipolar 3 processes
1 axon, others dendrites
Most common; major neuron in CNS
Bipolar 2 processes
1 axon and 1 dendrite
These are rare, eg., Retina and olfactory
Unipolar 1 short process
Divides T-like both branches considered axons
Distal (peripheral) process associated with sensory
receptor
Proximal (central) process enters CNS

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Table 11.1 Comparison of Structural Classes of Neurons (1 of 3)

Trigger zone - receptive region

of the cell

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Table 11.1 Comparison of Structural Classes of Neurons (2 of 3)

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Functional Classifications
Sensory
Transmit from sensory receptors to CNS
Almost all Unipolar
Cell bodies in ganglia in PNS eg DRG
Motor
Transmit from CNS to effectors
Multipolar
Most cell bodies in CNS (except some autonomic neurons)
Interneurons
Connect motor & sensory neurons
99% of body's neurons
Most confined in CNS

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Synapse
Neurons functionally connect by synapses
Axodendriticbetween axon terminals of one neuron
and dendrites of others
Axosomaticbetween axon terminals of one neuron
and soma of others
Or from one neuron to an effector cell
Less common types:
Axoaxonic (axon to axon)
Dendrodendritic (dendrite to dendrite)
Somatodendritic (dendrite to soma)

PLAY

Animation: Synapses

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Presynaptic neuron

Presynaptic neuron

Axodendritic
synapses
Dendrites

Axosomatic
synapses
Cell body
Axoaxonal
synapses

Postsynaptic neuron

Axon

Axon

Figure 11.16 Synapses.

Axosomatic
synapses

Cell body (soma)

of postsynaptic
neuron
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Varicosities

GREEN= Synapses
RED= neuron

Chemical Synapses
Utilise neurotransmitters
Typically
Axon terminal of presynaptic neuron

Contains synaptic vesicles filled

with neurotransmitter
Neurotransmitter receptor region
on postsynaptic neuron's
membrane
Usually on dendrite or cell body
Two parts separated by synaptic cleft
Fluid-filled space through which
transmitter
diffuses

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Electrical Synapses
Less common
Neurons electrically coupled
(gap junctions connect
cytoplasm of adjacent neurons)
Rapid communication (106 ions/
sec or greater
Uni or bi-directional
Synchronize activity (local
inhibitory networks)
Abundant in Embryo nervous
tissue
[occur in heart and gut ]

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Information Transfer : Chemical Synapses

AP arrives at axon terminal
Causes voltage-gated Ca2+
channels to open
Ca2+ floods into cell
Synaptotagmin protein binds
Ca2+ and promotes fusion of
synaptic vesicles with axon
membrane
Exocytosis of neurotransmitter
into synaptic cleft occurs
Higher impulse frequency
! more released

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30 50 nm

KNOW this slide

Chemical Synapses

Neurotransmitter diffuses across

synapse
Binds to receptors on
postsynaptic neuron
Often chemically-gated ion
channels
Ion channels are opened
Causes an excitatory or inhibitory
event (graded potential)
Neurotransmitter effects
terminated
- re-uptake
- enzymatic degradation
- diffusion away
Figure 11.17 Chemical synapses transmit signals from one
neuron to another using neurotransmitters.

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The Resting Membrane Potential

Potential difference across membrane of resting cell
70 mV in neurons (inside -ve relative to outside)
Actual voltage difference varies from -40 mV to -90 mV
Ions move, potentials of cell change.
Membrane termed polarized
Generated by:
Differences in ionic makeup of ICF and ECF
Differential permeability of the plasma membrane

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 2013 Pearson Education, Inc.

Resting Membrane Potential

ECF has higher concentration of Na+
Balanced by [Cl- ]
ICF has higher [K+ ] than ECF
Balanced by -ve charged proteins
K+ plays most important role in resting potential
Neuron membrane 25 X more permeable to K+ than Na+
(more leakage channels)
Impermeable to large anionic proteins
Slightly permeable to Na+ (via leakage channels)
Sodium diffuses into cell down concentration gradient
Potassium diffuses out of cell down concentration gradient
Membrane quite permeable to Cl

PLAY

A&P Flix: Resting Membrane Potential

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Excitatory vs Inhibitory actions

Depolarization
Decrease in resting membrane potential (toward 0 and
above)
Inside becomes less negative than resting membrane
potential
Increases probability of producing a nerve impulse
Hyperpolarization
An increase in membrane potential (away from 0)
Inside of cell more negative than resting membrane
potential)
Reduces probability of producing a nerve impulse

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Graded vs Action potentials

Membrane potential changes when
[ions] across membrane change
Membrane permeability to ions changes
Produce two types signals
Graded potentials
Incoming signals operating over short distances
Action potentials
Long-distance signals of axons

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Table 11.2 Comparison of Graded Potentials and Action Potentials

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Table 11.2 Comparison of Graded Potentials and Action Potentials

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Table 11.2 Comparison of Graded Potentials and Action Potentials

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Postsynaptic Potentials
Types
EPSP excitatory postsynaptic potentials
IPSP inhibitory postsynaptic potentials
EPSP

Neurotransmitter binding opens chemically gated

channels
Simultaneous flow of Na+ and K+ in opposite
directions
Na+ influx greater than K+ efflux ! net depolarization
called EPSP (not AP)
EPSP help trigger AP if EPSP is of threshold strength
Can spread to axon hillock, trigger opening of
voltage-gated channels, and cause AP to be
generated

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Membrane potential (mV)

Figure 11.18a Postsynaptic potentials

EPSP is a local
depolarization of the
postsynaptic membrane
that brings the neuron
closer to AP threshold

+30
0

Neurotransmitter binding
opens chemically gated
ion channels, allowing
Na+ and K+ to pass
through simultaneously.

Threshold
55
70
Stimulus
10
20
Time (ms)

30

Excitatory postsynaptic potential (EPSP)

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Membrane potential (mV)

Figure 11.18b Postsynaptic potentials

An IPSP is a local
hyperpolarization of the
postsynaptic membrane
that drives the neuron
away from AP threshold

+30
0

Threshold

Neurotransmitter binding
opens K+ or Cl channels.

55
70
Stimulus
10
20
30
Time (ms)
Inhibitory postsynaptic potential (IPSP)

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Synaptic Integration: Summation

A single EPSP cannot induce an AP

EPSPs can summate
IPSPs can also summate
Most neurons receive both excitatory and inhibitory
inputs from thousands of other neurons
Only if EPSP's predominate and bring to threshold
! AP

Types
Temporal summation
One or more presynaptic neurons transmit
impulses in rapid-fire order
Spatial summation
Postsynaptic neuron stimulated
simultaneously by large number of terminals
at same time
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E1

Membrane potential (mV)

Figure 11.19a Neural integration of EPSPs and IPSPs.

Threshold of axon of
postsynaptic neuron
Resting potential

55
70
E1

E1
Time

No summation:
2 stimuli separated in time
cause EPSPs that do not
add together.
Excitatory synapse 1 (E1)
Excitatory synapse 2 (E2)
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Inhibitory synapse (I1)

Figure 11.19b Neural integration of EPSPs and IPSPs.

Membrane potential (mV)

E1

0
Resting
potential

Threshold of
axon of
postsynaptic
neuron

55
70
E1 E1
Time
Temporal summation:
2 excitatory stimuli close
in time cause EPSPs
that add together.
Excitatory synapse 1 (E1)
Excitatory synapse 2 (E2)

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Inhibitory synapse (I1)

Figure 11.19c Neural integration of EPSPs and IPSPs.

E1

Membrane potential (mV)

E2
0
Resting
potential

Threshold
of axon of
postsynaptic
neuron

55
70
E1 + E 2
Time
Spatial summation:
2 simultaneous stimuli at
different locations cause
EPSPs that add together.
Excitatory synapse 1 (E1)
Excitatory synapse 2 (E2)

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Inhibitory synapse (I1)

Figure 11.19d Neural integration of EPSPs and IPSPs.

E1

Membrane potential (mV)

l1

Threshold of axon of
postsynaptic neuron
Resting potential

55
70
l1

E 1 + l1
Time

Spatial summation of
EPSPs and IPSPs:
Changes in membane potential
can cancel each other out.
Excitatory synapse 1 (E1)
Excitatory synapse 2 (E2)
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Inhibitory synapse (I1)

Integration: Synaptic Potentiation

Repeated use of synapse increases ability of
presynaptic cell to excite postsynaptic neuron
Ca2+ concentration increases in presynaptic
Calcium is necessary because it
terminal and postsynaptic neuron
is essential for release of
neurotransmitters
System is PRIMED
Brief high-frequency stimulation partially
depolarizes postsynaptic neuron
Chemically gated channels (NMDA receptors)
allow Ca2+ entry
Ca2+ activates kinase enzymes that promote
more effective responses to subsequent stimuli

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Integration: Presynaptic Inhibition

Neurotransmitter
release by one neuron
(usually excitatory
neuron) inhibited by
another neuron via an
axo-axonic synapse
Less neurotransmitter
released
Smaller EPSPs formed
Think of it as Volume
control

Neurotransmitters
60 neurotransmitters have been identified
Most neurons make two or more
neurotransmitters
Neurons can exert several influences
Usually released at different stimulation
frequencies
Classified by

Chemical structure
Function [excitatory versus inhibitory]
Type of receptor(s)
Actions direct (ion channels): indirect (2nd
messengers)

Gamma aminobutyric acid (GABA)

Glycine
Glutamate
Aspartate
Dopamine
Serotonin
Norepinephrine
Histamine
ATP
Acetylcholine
Angiotensin II
Corticotropin
Corticotropin Releasing hormone
Vasopressin
Beta-endorphin
Substance P
Neuropeptide Y
PPY
Bradykinin
Neurotensin
Somatostatin
Cholecystokinin
Gastrin
Secretin
Oxytocin
Nitric oxide
Carbon monoxide

Figure 11.20 Channel-linked receptors.

Ion flow blocked

Ions flow
Ligand

Closed ion
channel

Open ion
channel
Promotes rapid responses by altering membrane
potential
Examples: ACh and GABA

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Neurotransmitters: Indirect Actions

Through second messengers, usually G
protein pathways
Oversee slow synaptic responses
Broader, longer-lasting effects similar to
hormones
Biogenic amines, neuropeptides, and
dissolved gases

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Know something about

Figure 11.21 Indirect actions: G protein-inked receptors.

G protein signaling mechanisms are like a
molecular relay race

Ligand (1st Receptor

messenger)

G protein

Enzyme

1 Neurotransmitter
(1st messenger) binds
and activates receptor.

2nd
messenger

Adenylate cyclase

Closed ion channel

Open ion channel

Receptor
G protein

5a cAMP changes membrane

permeability by opening or
closing ion channels.

GDP

2 Receptor
activates G
protein.

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3 G protein
activates
adenylate
cyclase.

4 Adenylate
cyclase converts
ATP to cAMP
(2nd messenger).

5c cAMP activates
specific genes.

5b cAMP activates
enzymes.

Active enzyme

Nucleus

Channel-Linked (Ionotropic) Receptors

Ligand-gated ion channels
Action is immediate & brief
Excitatory receptors are channels for small cations
Na+ influx contributes most to depolarization
(Glutamate)
Inhibitory receptors allow Cl influx that causes
hyperpolarization (GABA)

HA DA NA 5HT
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Glutamate

Action Potentials (AP)

Occur in axons of
neurons (and muscle
cells)
A brief reversal of
membrane potential
with a change in
voltage of ~100 mV
Do not decay over
distance as graded
potentials do

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Have to know that

1,2,3,4,5 is a typical
action potential

Figure 11.11 The action potential (AP) is a brief change in membrane potential in a patch of
membrane that is depolarized by local currents

1 Resting state. No

2 Depolarization

Membrane potential (mV)

ions move through

voltage-gated
channels.

is caused by Na+
flowing into the cell.

3 Repolarization is

caused by K+ flowing
Repolarization resets electrical
out of the cell.

conditions, not ionic conditions

After repolarization, Na+/K+ pumps
(1000 s of them in axon) restore ionic
conditions

+30
3
4 Hyperpolarization is

Threshold

55
70

PLAY

2
3
Time (ms)

voltage at which the

AP is triggered

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caused by K+ continuing to
leave the cell.

Action
potential

A&P Flix: Generation of an Action Potential

AP: Depolarizing Phase

Depolarizing local currents open voltage-gated Na+
channels
Na+ rushes into cell
Na+ influx causes more depolarization which opens
more Na+ channels ! ICF less negative
At threshold (55 to 50 mV) positive feedback causes
opening of all Na+ channels ! a reversal of membrane
polarity to +30mV
Spike of action potential

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AP: Repolarizing Phase

Repolarizing phase
Na+ channel slow inactivation gates close
Membrane permeability to Na+ declines to resting
state
AP spike stops rising
Slow voltage-gated K+ channels open
K+ exits the cell and internal negativity is restored

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Propagation of an AP
AP s are self-propagating
Na+ influx causes local currents
Local currents cause depolarization of adjacent
membrane areas in direction away from AP origin
(toward axon's terminals)
Local currents trigger an AP there
This causes the AP to propagate AWAY from the AP
origin
Since Na+ channels closer to AP origin are inactivated no
new AP is generated there
Propagation in myelinated axons differs

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Figure 11.15 Action potential (AP) propagation in nonmyelinated and myelinated axons.
Stimulus

Size of voltage

In bare plasma membranes, voltage decays.

Without voltage-gated channels, as on a dendrite, voltage decays because
current leaks across the membrane.
Stimulus

Voltage-gated
ion channel

In nonmyelinated axons, conduction is slow (continuous conduction).

Voltage-gated Na+ and K+ channels regenerate the AP at each point along the axon, so
voltage does not decay. Conduction is slow because it takes time for ions and for gates
of channel proteins to move, and this must occur before voltage can be regenerated

Stimulus
Myelin
sheath

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Myelin
sheath

Myelin
sheath gap
1 mm

In myelinated axons, conduction is fast (saltatory conduction).

Myelin keeps current in axons (voltage doesn t decay much). APs are generated only
in the myelin sheath gaps and appear to jump rapidly from gap to gap

CNS determines stimulus

intensity by the frequency
Higher frequency =
stronger stimulus

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70

voltage

Strong stimuli cause APs to

occur more frequently

Action
potentials

+30

Stimulus

APs are independent of

stimulus intensity
How does CNS tell
difference between a
weak stimulus and a
strong one?

Membrane
potential (mV)

Stimulus Intensity

Threshold

Stimulus

0
Time (ms)
Figure 11.13 Relationship between stimulus
strength and action potential frequency

Neural Integration
Neurons function in groups
Groups contribute to broader neural functions
There are billions of neurons in CNS
integration allows the individual parts to become a
smoothly operating whole
Circuits
- Patterns of synaptic connections in neuronal
pools
- Four types of circuits
Diverging
Converging
Reverberating
Parallel after-discharge

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