1. Excitable properties
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The University of Toledo
College of Health Science and Human Service
Spring 2011
OCCT702 & PhyT507
Neuroscience
Alexia E. Metz, Ph.D., OTR/L
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Excitable properties of neuronsAction potentials are electrical impulses that are generated by neurons.
They (APs) are conducted along axons toward the nerve terminal.
At the nerve terminal they cause the release of neurotransmitter into the
synapse.
NT crosses the synapse to act on the postsynaptic neuron.
The action of NTs can be very fast & time delimited or slow & lasting.
Synaptic communication also can be modified, which may underlie
learning & memory (even rehabilitation).
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Excitable properties of neurons
Fundamental principles
Resting membrane potentials
Excitability
Action potentials
Graded potentials
Demyelinating diseases
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Fundamental principles
Gradients & diffusion
Ions
Ohms law Electrical potential & capacitance
Electrical current
Resistance/conductance Electrochemical gradient
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Chemical gradients & Diffusion
time
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Electrical potential
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Electrical potential Separation of charge creates the drive for charges to flow toward
each other
The ability to store charge = capacitance
The movement of charge = current
The amount of current that can flow is limited by resistance
The amount of current that can flow is the conductance
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Ohms law
V=IR
V
I R
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Ohms law plotted
Equation of a
line:
y = mx + b
Conductance
is the inverseof resistance:
g=1/R
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Electrochemical gradient
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Resting membrane potential
Membrane & Membrane proteins
RMP
Nernst potentials
GHK model
The words we use
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Important cellular molecules
Phospholipids
Proteins
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Unequal distribution of ions
Proteins in the membrane workto create chemical gradients of
ions across the membrane.
Best studied example:
Sodium potassium exchange pump
which
extrudes sodium ions (Na+) andbrings in potassium ions (K+),
Creating an imbalance
Ion inside
(mM)
Outside
(mM)
K+ 140 5
Na+ 5-15 145
Cl- 4 110
Ca2+ 1X10-4 2.5-5
Ion concentrations in a typical mammalian cell
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Ion channels let ions move across
the membrane
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Ion channel selectivity
Na+K+
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Types of ion channels, defined by what makes them open
Non-gated channels (Leak channels)
Voltage-gated channels
Ligand-gated channels
Modality-gated channels
Potassium rules!
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Potassium rules!
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Potassium (K+ ) leak:
K+ concentration is higher inside the cell.
K+-selective proteinaceous pores allow some K+ to leave along its concentration gradient,
creating a relative negative charge inside the cell.
Some K+ is attracted back by the negative charge.
Movement in the two directs stops once an equilibrium is met.
The membrane potential at which this occurs is the Equilibrium Potential. This is predicted by a
mathematical equation, the Nernst equation.
EK= 62 log ([K]out )
([K]in)
Because the membrane is more
permeable to K+
than to other non-equally distributed ions, the
equilibrium potential for K+ has the
largest influence over the resting
membrane potential.
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Goldman-Hodgkin-Katz model
Nernst potential for each ion species: K+: -90 mV Na+: +60 mV Cl-: -90 mV Ca2+: +145 mV
Real-time relative permeability of the membrane to eachion species dictates the compromise reached in thepotential (works like a weighted average)
Driving force = the farther from the equilibrium potential,the more intense the push for the ions to flow across themembrane
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Polarity of membrane potential
time
Resting membrane potential
-65 mV
in most mammalian neurons
depolarization,
excitation
hyperpolarization,
inhibition
K+ reversal
Na+reversal
-90 mV
+60 mV
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Action Potentials!!!
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Types of ion channels, defined by what makes them open
Non-gated channels (Leak channels)
Voltage-gated channels
Ligand-gated channels
Modality-gated channels
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States of voltage-gated channels
Open/
Activated
Inactivated RecoveredClosed
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Action potential:
Voltage-gated sodium channels
time
RMP
-65 mV
Depolarization (to ~ -45 mV) activates Na+ channels
Na+ ions enter / leave the cell
The membrane potential depolarizes / repolarizes
The sodium channels dont stay open indefinitely,
but instead inactivate
K+ reversal
Na+reversal
-90 mV
+60 mV
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Action potential:
Voltage-gated potassium channels
time
RMP
-65 mV
Depolarization (to ~ -45 mV) activates K+ channels,
but they are much slower in opening so by the time they do
the membrane potential is ~+60 mV
K+ ions enter / leave the cell
The membrane potential depolarizes / repolarizes
Potassium channels stay open so the membrane potential
hyperpolarizes, but then they inactivate too
K+
reversal
Na+reversal
-90 mV
+60 mV
A ti t ti l
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time
Action potentials:
putting it all together
Na+ reversal, +60 mV
0 mV
resting membrane potential, -65 mV
K+ reversal, -90 mV
depolarizing input,Na+ channels open
(activate) threshold
K+ channelsactivate
K+ channels
close (deactivate)
Na
+
channels close(inactivate)
Depolarization
Hyperpolarization
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Another look at the action potential
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Propagation of the action potential
down the axon
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Myelin promotes AP propagation
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Action potential conduction
Faster in larger axons
Aided by myelination
Requires regular boosting by voltage-gated ion channels
Probably successfully continues down all
paths after a branch point
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Action potential firing patterns
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Changes in membrane potential
Action potentials
All-or-nothing
Stereotyped
Do not decrease with distance or time
Graded potentials
Variable size and duration
Decrease with distance and time
T f i h l d fi d b h t k th
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Types of ion channels, defined by what makes them open
Non-gated channels (Leak channels)
Voltage-gated channels
Ligand-gated channels
Modality-gated channels
Th ti t ti l t l t th
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The action potential travels to the synapse
and causes the release of neurotransmitter
onto post synaptic cells
Called a buton
Li d t d h l t ti ll
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Na+K+
Time (ms)
Membranepo
t ential
(mV)
Ligand-gated channels on post synaptic cells
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Summation
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Local potentials degrade
Disturbances of
membrane potential
can be carried along
membrane: Degrade with time and
distance
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Types of ion channels,
defined by what makes
them open
Non-gated channels (Leak channels)Constitutively open,
Dictate membrane potentialCan be modified so that they shut
Ligand-gated channelsOpen under the influence of neurotransmitter-receptor binding,Make neuron receptive to input from other cells
Voltage-gated channelsOpen under the influence of electrical charge across the membraneUnderlie action potentials
Modality-gated channelsOpen under mechanical influence (stretch, touch, pressure)
Make neuron receptive to environmental conditionsWe will talk about these more in the motor & sensory sections of the course
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What would happen if..
Oligodendrocytes or Schwann cells died?
Action potentials may fail to propagate down the entire length of the axon to the synapse.
Demyelinating diseases
CNS: multiple sclerosis
PNS: Guillain-Barre syndrome
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Multiple Sclerosis
One hypothesis: The immune system producesantibodies that attack oligodendrocytes.
Axons loose their myelination & scar tissue is leftbehind = plaques. These are diagnostic inclinical imaging.
Nerve conduction is drastically slowed orstopped.
Eventually, axons themselves degenerate.
Multiple Sclerosis
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Multiple Sclerosis
Symptoms of MS are unpredictable and vary from
person-to-person and from time-to-time in the same
person. This is because all myelinated central axons
are potential targets of the disease.
Four clinical courses: Relapsing-Remitting (85% of cases)
Primary-Progressive (10% of cases)
Secondary-Progressive
(50% of relapsing-remitting cases
transition to this course)
Progressive-Relapsing (5% of cases)
http://www.nationalmssociety.org time
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http://www.nationalmssociety.org/http://www.nationalmssociety.org/ -
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Multiple SclerosisScientists are investigating several different
strategies for stimulating the repair ofmyelin:
Antibodies,
Surgical replacement of damaged
oligodendrocytes and nerve cells, and
Replacing the cells that are damaged by
MS. Possible sources include:stem cells
skin-derived cells,
bone marrow andumbilical cord blood cells,embryonic cells,
adult brain cells, andSchwann cells from the PNS.
Blocking potassium channels.
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Multiple Sclerosis
Treatment:
symptom management
disease modification
(immune suppressionor modulation)
rehabilitation
Title:Cow Barn
City:West Hartford, CTArtist:Mary Beth Whalen
Sponsor:Guida's Milk & Ice Cream
Auction Beneficiary:
National Multiple Sclerosis Society
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