lecture on resting membrane potential by dr roomi.ppt

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  • 7/30/2019 Lecture on Resting membrane potential by Dr Roomi.ppt

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    Resting Membrane Potential (RMP)

    Dr. Mudassar Ali Roomi (MBBS, M. Phil.)

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    Important channels or carriers involved in the

    electrical activity of the cell

    Na+, K+ Leak channels: these are open all the

    time. Involved in generation of resting

    membrane potential (RMP).

    Gated channels: these channels open and close

    at a specific time when needed. Not open all the

    time. All of the gated channels are closed at RMP1. Voltage gated channels e.g. voltage gated

    sodium, potassium, calcium channels.

    2. Ligand gated channels e.g. Acetylcholine

    gated channels at neuromuscular

    junctions.

    Sodium-potassium ATPase pump: it works all

    the time. Also contributes to generation of

    resting membrane potential.

    NUTSHELL: Both leak channels and Na+/K+

    pump are active at rest ***

    17 January 2013 2

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    Resting Membrane Potential

    Definition: it is the potentialdifference across cell membraneat rest:

    it is negative inside with respectto outside.

    Potential values of RMP vary in various

    excitable tissues:

    In nerve fiber: -90 mV

    In skeletal muscle: -90 mV

    In cardiac muscle: -85 mV SA node: -55 mV

    In nerve cell body: -70 mV

    In smooth muscle: -55 mV to -60mV

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    Mechanism of

    Generation of RMP

    1. Contribution of thePotassium DiffusionPotential (-94 mVolts)

    2. Net Contribution ofSodium DiffusionThrough the NerveMembrane (+8 mVolts)

    3. Contribution of theNa+-K+ Pump (-4mVolts)

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    Mechanism of Generation of RMP

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    Mechanism of regulation of RMP

    Another factor is Na+-K+ pump (active all the time).

    Pumps out 3 Na+ ions &

    Pumps in 2 K+ ions.

    So more electro-positive ions are pumped out &

    contributes to RMP.

    As membrane is more permeable to K+ at rest, &

    much ionic diffusion, so large amount of K+ shouldmove out, but net movement is not much. Why???

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    Mechanism of regulation of RMP

    This is because when K+ moves out, anions(non-diffusible: proteins, organic phosphate &organic sulfate anions) attract them back.

    But this movement is sufficient to causerelative electro-negativity inside themembrane.

    Out of -90mV, -86mV is due to K+

    outflux &-4 mV is due to Na+ K+ pump.

    What is the evidence???

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    Evidence of major contribution to RMP by

    K+ ion:

    If we change, [K+] in ECF RMP is disturbed.

    If there is hypo-kalemia in ECF RMP will becomemore negative due to more potential difference

    hyper-polarization (more K+ leak out than restinglevel).

    If there is hyper-kalemia RMP becomes lessnegative hypo-polarization.

    But changes in [Na+] in ECF has no significant effecton RMP.

    We can also prove this by Nernst Equation.

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    Nernst Equation

    EMF (mV) = +/- 61 log conc inside / conc outside

    Assume that at rest, cell membrane is highlypermeable to Na+, then:

    -61 log 14/140

    (- for Na+ & K+ & + for Cl-)

    = -61 log 0.1

    = -61 x -1

    = + 61 mVSo potential difference across cell membrane should be+61mV, which is wrong.

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    Assume that at rest, cell membrane is highly

    permeable to K+, then:

    - 61 log 140 / 4

    = -61 log 35

    = -61 x 1.54

    = -94 mV So this assumption is correct that at rest, cell

    membrane is highly permeable to K+.

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    Goldman Hodgkin-Katz Equation

    EMF (mV) =

    - 61 log C Na+ i P Na+ + C K+ i P K+ + C Cl-o P Cl-

    C Na+ o P Na+ + C K+ o P K+ + C Cl-i P Cl

    -

    WITH GOLDMAN EQUATION SUMMATED POTENTIAL = -86 mV

    (C = CONCENTRATION, P= PERMEABILITY)

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    K+ Na+ leak channels are highly permeable to

    K+ but there is some inward movement of Na+

    + 8 mV potential is generated.

    -94 mV is due to K+ efflux

    + 8 mV is due to Na+ influx

    -94 + 8 = -86 mV = Goldman potential

    -4 mV is due to Na+ K+ pump

    -86 4 = -90 mV = RMP.

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    UNITS OF EXCITABILITY

    1. RHEOBASE

    2. UTILIZATION TIME3. CHRONAXIE

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    RHEOBASE, UTILIZATION TIME, CHRONAXIE

    RHEOBASE: Voltage /strength of stimulusrequired just to excite thetissue, e.g., 1 mV.

    UTILIZATION TIME: The time

    for which Rheobase mustbe applied to excite thetissue.

    CHRONAXIE: A time forwhich a stimulus, double

    the rheobase when applied,just excites the tissue, e.g.,2 mV. (Chronological is fromtime).

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    CLINICAL APPLICATION / SIGNIFICANCE OF

    CHRONAXIE

    A particular value of it for a particular tissue.

    Type A nerve fiber has minimum value of chronaxie,

    i-e., they are more excitable as compared to cardiacmuscle. (less chronaxiemore excitability)

    In nerve injury repair procedureWe assess therecovery by finding chronaxie of nerve effected &muscle effected.

    It improves with recovery. Damage to nerve fiber is determined by measuring

    chronaxie.