Neurophys.... Membrane Potential

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    Outline

    Resting membrane potentials

    Action potential

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    RMP

    Definition

    It is a steady state potential which exists acrossthe cell membrane

    It is always hyperpolarized

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    RMP

    SA node -60 mv

    Atrium -90mv

    Ventricles -90 mv

    Skeletal muscles -70mv

    Smooth muscle -60mv

    Peripheral nerves -70 mv

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    RMP

    Determinants of RMP?

    Electrolyte

    Na/K ATPase pump Intracellular protein

    Gibbs Domann

    Concentration gradient

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    RMP

    Electrolytes / concentration gradients

    ICF ECF

    Na 10-20 135-145

    K 150 3-5

    Cl 10-20 110

    100x

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    RMP

    The membrane is more permeable to Na and K ,so these ions tend to leak across the membranedown according the concentration gradient

    The membrane is 100 times more permeable to K So, there is more K is lost from the cell than Na

    enters to the cells

    Therefore, net result-larger amount of positive

    charges has left the cell than entering it.

    Thus, that is why cell are semipermeable

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    Na/K ATPase pump

    It pumps more Na out from the cell than K ispumped in

    ( 3Na out: 2K in)

    It maintains the RMP

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    Intracellular protein

    There are negatively charged intracellularly

    So RMP is negative

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    Gibbs- Donnan effect

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    The Donnan Effect

    Which fluid compartments are high in protein?

    intracellular fluid plasma

    Which fluid compartment is low in protein? interstitial fluid

    Fig. 1-27 Ganong

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    The Donnan Effect

    Proteins are impermeant polyanions.

    Proteins are impermeant to the membrane.

    due both to size and charge

    Most proteins have a net negative charge.

    This negative charge is balanced by cations, typically

    monovalent cations. K+for intracellular fluid

    Na+for plasma

    Fig. 12.11

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    The Donnan Effect

    When Donnan and Gibbs analyzed the situation

    mathematically, they showed that in and outcould not be in electrochemical and osmoticequilibrium at the same time.

    (see Ganong)

    As a result of the osmotic imbalance, water will

    flow into a compartment (cytosol, blood plasma)

    that contains more protein. The portion of the osmotic pressure that is due to the

    effects of protein is called colloidal osmotic pressure.

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    The problem:Because of theDonnan effect, cellswill swell and burst.

    The solution:

    For animal cells, thesodium pump solves

    the problem. Na+pumped out

    Cl-follows Na+

    H2O follows NaCl

    Alberts et al.,Molecular Biology of the Cell

    Animal cells must

    have sodium pumps.

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    Nernst Equation

    at equilibriumthese opposing energiesmust be equal

    therefore by rearrangement, viz. Calculate one ion

    o

    im

    K

    K

    zF

    RTE

    ln

    E

    K

    KK

    i

    o

    615. log

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    GOLDMAN CONSTANT-FIELD EQUATION

    V = RT In PK+[K+]o + PNa+[Na

    +]o + PCl- [Cl-]i

    F PK+[K+]i + PNa+[Na

    +]i + PCl- [Cl-]o

    The magnitude of the membrane potentialat any given timedepends, of course, upon the distribution of Na+, K+ and Cl-and the permeability of the membraneto each of these ions.

    It calculate 3 ions

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    THE ACTION POTENTIAL

    An action potential is the sequence ofchanges in the membrane potential thatoccurs during the transmission of anelectrical signal along the cell membrane,as measured at a specific point on a nerve

    or muscle cell membrane.

    depolarization

    repolarization

    ~ 1 ms

    Fig. 12-13

    Fig. 2-6Ganong

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    The Action Potential

    skeletal muscle fibers

    axons of neurons

    Fig. 12.13

    Fig. 12.12Fig. 11.1

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    Phase 1 whn a nerve is stimulated, it initiates

    the ligand-gated Na channels, n there will beinflux of Na ions initiating depolarization

    Phase 2 whn the depolarization reaches thethreshold potential ard -55mV, it opens up thevoltage gated fast Na channels

    Phase 3- massive influx of Na ions

    Phase 4 the potential overshoots the

    isopotential line to ard + 30mV ( positive spikeAP)

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    Phase 5 Na channels closed, K channelsopen , and there will be K efflux

    Repolarization

    Phase 6 due to continuation of K efflux ,there will be hyperpolarization

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    Action Potentials

    Characteristics:

    1. Stereotypical size and shape2. Propagation to adjacent sites

    3. All-or-none response

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    Action Potentials:

    Characteristics1. Stereotypical size and shape

    Each action potential for any cell type looks identical.

    It depolarizes to the same potential.

    It repolarizes back to the same resting potential.

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    -70 mV

    0 mV

    1.0 2.0

    Action Potential

    Resting membrane potential

    Time (milliseconds)

    Voltage

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    Action Potentials :

    Characteristics2. Propagation to adjacent sites

    The action potential moves along the axon in a wave of

    changing membrane potential. After an action potential, the membrane is in a

    refractory state so the propagation is in one directiononly.

    This action potential propagates from one end of thenerve to the other.

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    A

    B

    C

    -+

    -+

    -+

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    +

    -

    Activeregion

    Propagation of action potentials(in unmyelinated fibres)

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    Myelin sheath

    Action potential

    Node of Ranvier

    -+ -

    + +-

    +- +

    - -+

    Saltatory conduction in myelinated fibres

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    2

    4

    6

    8 myelinated

    unmyelinated

    Effect of myelination on speed of propagation

    Fibre diameter (m)

    Conductionvelocity(m

    /s)

    1 2 3 4

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    Action Potentials :

    Characteristics3. All-or-none response

    If an excitable cell is depolarized to threshold in a

    normalmanner, then the occurrence of an actionpotential is inevitable.

    On the other hand, if the membrane is not depolarizedto threshold, no action potential can occur.

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    -100

    -50

    0

    +50

    Threshold potential

    Resting membrane potential

    Increasing subthreshlod stimuli

    Membranepotential(mV)

    Time|----------------|

    1 ms

    All-or-none action potential

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    Compound action potentials

    Peripheral nerves contain a mixture of fibres

    Classified according to

    Function

    Diameter

    Conduction velocity

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    Table of compound action potential

    Fibre Function Diameter

    (m)

    Conduction

    velocity

    (m/s)

    A

    Skeletal motor, joint position

    Touch, pressure

    Muscle spindle motor

    Pain, temperature touch

    10-20

    5-10

    3-6

    2-5

    60-120

    40-7-

    15-30

    10-30

    B Preganglionic autonomic 1-3 3-15

    C Pain 0.5-1 0.5-2

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    Voltage

    (V)

    Time (ms)

    Compound action potential

    A

    B

    C

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    The electrical signals generated by the action

    potentials can be sensed using skin or needleelectrodes placed near the muscle. This is thebasis of electromyography.

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    Electroencephalography

    Is recording of spontaneous activity of thebrain

    Generated by pyramidal cells in cortical layers1, 2 and 5

    Its a summation of excitatory and inhibitory

    postsynapticpotentials in pathways running

    from thalamic nuclei to cortex.

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    Eeg

    4 types of waveform :

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    Occurs Hz Voltage(microv)

    beta Fully awakeMaybe also produced by volatile

    and IV anaesPrecentral cortex

    15-25 20

    alpha TransitionalAwake,relaxed with eyes closedOccipital cortex

    10-15 20-50

    theta SleepOccurs in children, elderlyMay indicates dysfx of drugs

    1-5 20-50

    delta Occurs during sleep during stage3 and 4 of NREM

    0.5 1 >50

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    Application of EEG

    In tumor and epilepsy shows high voltagespike waves

    Cerebral infarcation low volatge and low

    frequency Thiopentone, propofol, etomidate, and

    volatile agents produce initial fast frontalbeta, then frontal alpha spikes with highampitude , then 1-3 HZ delta burstsuppression with high amplitude , then noisoelectric EEG

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    Application of EEG

    Ketamine frontal rhythmic delta with highamplitude, then intermittent, polymorphicdelta with large amplitude interspersed withlow amplitude beta. NO EEG silence

    BZD- no burst suppression and no isoelectricEEG

    Opiods dose related low frequency andhigh amplitude, no isoelectric EEG

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    Sleep

    Is a state of unconsiousness from which aperson can be aroused by a sensorystimulation

    Involves decrease activity of RAS(reticularactivation system)

    2 stages :

    NREM or slow-wave sleep(4 stages)

    REM( tonic and phasic)

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    Stages of sleep

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    Influence of anaesthesia and

    surgery during sleep NREM anaesthetic stages REM- post op complication

    Why???? In NREM, mainly is by parasympathetic In REM, esp during the phasic phase is mainly by

    sympathetic and is predominant during post op Day1

    In REM, thr wil be impaired resp fx

    Maldistribution of ventilation , impaired V/Q matchingwhich lead to arterial hypoxemia

    Thus, MI, cerebral impairment and hypoxemia iscommon post op Day 1

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    Depth of anaesthesia for

    awareness Awareness Inadvertent return to conciousness during a supposed

    GA with or without recall

    Techniques that monitored depth ofanaesthesia: MAC

    BIS(bispectral index)

    Vital sign Entropy

    TCI/TIVA ( plasma concentration drug)

    IFT(isolated forearm tech)

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    BIS

    It monitors record raw EEG which altersanaesthesia and after processing produces adimensionless number from 0 -100 which is

    an index of probability that the pt is aware

    Put at the frontal lobe

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    Limitation of BIS

    Site of operation

    Cant do in children

    Organic brain lesion

    Psy problem

    Drugs like etomidate and ketamine

    Costly Artifacts by surgery

    diathermy/cauterization/vibration