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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    -

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    --

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    -++

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    0negative positive

    Electrical potential

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    -+

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    0negative positive

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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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