Transcript action potential

Physiology of Neurons
• Reading Assignment: Textbook of Medical
Physiology, 12th edition, Guyton & Hall
• Chapters 45 & 46, pp. 543-570
• Recommended reading: Chapter 11 from Boron
& Boulpaep Medical Physiology
Morphology of a Typical Neuron
Blumenfeld, Neuroanatomy
Myelin sheaths of axons
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
A. Myelinated axons in the central
nervous system. A single
oligodendrocyte (G) emits several
processes, each of which winds in a
spiral fashion around an axon to
form the myelin sheath.
B. Myelinated axon in the peripheral
nervous system. A Schwann cell
forms a myelinated sheath for
peripheral axons in much the same
fashion as oligodendrocytes do for
central ones, except that each
Schwann cell myelinates a single
axon.
Berne & Levy, Physiology, 5th Ed.
The major light
and electron
microscopical
features of neurons
Purves et al., Neuroscience 4th Ed.
Neuron – the axon
Boron &
Boulpaep,
Medical
Physiology
• Projects from the cell body at the site of the axonal hillock (or initial
segment)
• Carries impulse away from the cell body
• May be myelinated or not myelinated
• Contains numerous Na+ channels
Axonal Degeneration
and Regeneration
Step 1: Degeneration of
synaptic terminal
distal to lesion
Step 2: Wallerian
degeneration
Step 3: Myelin
degeneration
Step 4: Scavenging of debris
Boron & Boulpaep, Medical Physiology
Axonal Degeneration
and Regeneration
Step 5: Chromatolysis
Step 6: Retrorade
transneuronal
degeneration
Step 7: Anterograde
transneuronal
degeneration
Berne & Levy,
Physiology 5th
Ed.

The rate of regeneration is limited by the rate of slow
axonal transport to about 1 mm/day.
Neuronal
Cytoskeleton
Is important for
transport, maintaining
shape/structure, and
compartmentalizing
the cell



Microtubules
Neurofilaments
Microfilaments
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Axonal Transport
Transport type
Speed
(mm/day)
Fast anterograde ~400
Fast retrograde ~200-300
Mechanism
Material Transported
Kinesin
Dynein
Slow
anterograde
Unknown
Mitochondria, vesicles
Degraded vesicular
membrane, absorbed
exogenous material
Cytoskeletal elements,
soluble proteins, actin
~1-5
Shingles
• After infection with chickenpox the varicella-zoster virus
becomes dormant in dorsal-root ganglia, only to reactivate later
when the immune system no longer contains it. Such
containment failures are more likely with age and with
immunocompromised states, and this produces the classic
appearance of shingles in a dermatomal distribution.
• It may also cause postherpetic neuralgia, a disabling condition of
chronic pain that is difficult to manage.
• Herpes Simplex Virus Type 1 capsid protein VP26 interacts with
Dynein Light Chains RP3 and Tctex1 and this plays a role in
viruses retrograde cellular transport.
Peripheral
Nerve
Boron & Boulpaep, Medical Physiolog
As an antioxidant, Vitamin E supports normal peripheral nerve
function by preventing damage to Schwann cells and dorsal
root ganglia
Neuron – the presynaptic terminal
Boron & Boulpaep, Medical Physiology
Myasthenia Gravis
Is an autoimmune disease in which antibodies bind to acetylcholine receptors
at the neuromuscular junction, thereby disrupting their functionality and
causing them to be more rapidly degraded
The weakness is characterized by rapid tiring of the muscle with repeated use
Median age range of onset is 15-35 years of age
Fatigue and eye muscle weakness are the prominent symptoms of the disease
Patients are treated with acetylcholinesterase inhibitors to increase the
concentration of ACh in the synapse. A higher concentration increases the
probability that ACh will bind to its receptors.
IV administration of edrophonium or neostigmine, drugs that block the
breakdown of acetylcholine by acetylcholinesterase, temporarily increases the
levels of acetylcholine at the neuromuscular junction.
Depolarization
• Excitatory input to a neuron usually generates a flow
of positive charge across the dendritic membrane
• Because the interior of a resting neuron is polarized
negatively, this inward current depolarizes (makes
the membrane voltage more positive) the cell
ACTION POTENTIAL
Boron & Boulpaep, Medical Physiology
Basic
Properties
of Action
Potentials
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Response to a Stimuli
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Changes in Ionic Conductance
During Action Potential
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Signal Conduction in Dendrites
• The change in membrane potential (Vm) caused by a
neurotransmitter at the postsynaptic membrane is called
postsynaptic potential (PSP).
– If the neurotransmitter is excitatory, it produces a
depolarizing Excitatory PSP (EPSP).
– If the neurotransmitter is inhibitory, it produces a
hyperpolarizing Inhibitory PSP (IPSP).
Excitatory Post Synaptic Potentials
1.
Postsynaptic increase in sodium or calcium conductance,
2.
Postsynaptic decrease in potassium conductance,
Na - most prevalent - leads to depolarization just as for action potential
Both increase the positive charge in the cell = EXCITATORY
Inhibitory Post Synaptic Potentials
Increased potassium efflux or chloride influx,
Both decrease the positive charge in the cell = more
negative = INHIBITORY
Boron & Boulpaep, Medical Physiology
Spatial vs
temporal
summation
of ESPSs
Spatial summation is the adding together of EPSPs or IPSPs over SPACE
Temporal summation is the adding together of EPSPs and IPSPs over TIME
Attenuation of EPSPs in dendrites
The thicker and shorter the
dendrite, the more likely is
a dendritic EPSP to
trigger an action potential
at the axon hillock
Boron & Boulpaep, Medical Physiology
Dendritic Membranes Have VoltageGated Ion Channels
• In Cerebellar Purkinje cells, the dendrites may fire slow
Na
Ca2+ actionTTX:
potentials
and can propagate toward the
channel
soma, but do
not continue down the axon.
blocker
• These slow Ca2+ action potentials may trigger fast Na+dependent action potentials in the soma and initial
segment.
Boron & Boulpaep, Medical Physiology
Ca2+ and Na+ action potentials
Dendrites usually do not
fire AP, however in
Purkinje cells the high
density of voltage- gated
Ca2+ channels in the
dendrites allows the
generation of slow
dendritic Ca2+ spikes,
which propagate to the
axon soma
TTX: Na
channel
blocker
Ca2+ spikes
are the ones
that generates
rhythmic burst
Boron & Boulpaep, Medical Physiology
Some neurons generate
spontaneous spiking activity, even
without dendritic input (i.e.,
magnocellular neurons of
hypothalamus)
The key for this type of behavior is
ion channels with slow kinetics (e.g.,
Ca2+ channels) in addition to those
with the typically fast kinetics (e.g.,
Na+ channels).
The neuron's response to dendritic inputs varies in both the shapes of
single action potentials and different repetitive firing patterns
• A = do not adapt
Na and K channels
• B = adapt strongly
Na and K channels
another set of K channels
(activate very slowly)
• C = rhythmic bursts
Most dendrites are low-pass filters:
decrease high frequency/rapidly
changing signals more than low
frequency/steady signals
steady, strong input
Repetitive
spiking
patterns of
neurons
Boron &
Boulpaep, Medical
Physiology
Axonal Conduction
Axons are specialized for rapid, reliable, and efficient transmission of
electrical signals
Myelinated axons are specialized for reliably and rapidly carry
electrical signals from one place to other places, in the form of action
potentials
An action potential starts at the initial segment due to high density of
voltage-gated Na+ channels.
All-or-none principle:
A neuron fires with the same potency each time
Frequency for firing can vary
It either fires or not; it cannot partially fire
Can travel very long distances -self-propagating
Action potentials from different parts of a neuron
Low threshold at
the initial
segment >>
high density of
Na channels
Boron & Boulpaep, Medical Physiology
Axons vary in diameter, and may have
myelin
Conduction velocity
of a myelinated
axon increases
linearly with
diameter
Axons are larger than
about 1 m in
diameter are all
myelinated
Myelinated axons
Single live axons
Cross-section by EM
•
•
Demyelinization
Remember unmyelinated and demyelinated are different !!
Demyelinated axons conduct action potentials slowly,
unreliably, or not at all
Demyelinating diseases of the CNS: Multiple sclerosis,
progressive multifocal leukoencephalopathy,
central pontine myelinolysis
Demyelinating diseases of the peripheral nervous system:
Landry-Guillain-Barre syndrome
Demyelination usually does
not kill the axon itself
Demyelination
Boron & Boulpaep, Medical Physiology
Multiple Sclerosis (MS):
The most common demyelinating disease of
the central nervous system.
An autoimmune disease directed against the
myelin or oligodendrocytes.
Unclear trigger, more common in women than
in men
Multiple Sclerosis (MS):
Characteristic of many patients with MS is remissions and
relapses
 An exacerbation is due to the occurrence of active
inflammation of a white matter tract in the CNS.
 A remission occurs when the inflammation subsides and the
demyelinated axons recover some of their function, and are
able to conduct action potentials through the area of myelin
damage.
Demyelinating Disease of the
Peripheral NS
• Landry-Guillain-Barre Syndrome:
– Following a respiratory, or other viral or mycoplasmal
infection, an ascending neurologic syndrome develops
– Starts with weakness, leads to paralysis of the legs and
subsequent involvement of the hands and arms
It may involve the paralysis of the nerves feeding the brain stem
which requires mechanical ventilation
Initial stage reaches a plateau, then gradually resolves
Pathology: segmental demyelination in PNS