Meeting 14 & 15

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mse263
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148155
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Meeting 14 & 15
Updated:
2012-04-18 18:16:58
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MCBII Exam
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resting membrane potential/channels
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  1. Nernst Equation
    E(ion) = RT/ZF*(ln)[ionext]/[ionintra]

    • -R=gas constant (8.31 K-1mol-1)
    • -T=abs. temp (293 K @ 20 C)
    • -Z= charge of ion
    • -F= Faraday constant (23062 cal/mol*V)

  2. outside/inside is reversed in the case of Cl
  3. inside of cell:
    • -inside: potassium (K+)
    • -outside: sodium (Na+)
    • -Cl- (as you can see) is mostly outside the cell; the major negative ion INSIDE the cell is P- (from organic molecules)

    -resting potential depends mostly on K+: -70 mV
  4. conductance
    Em - ENa = equilibrium potentials (solve for these using Nernst?)

    -membrane potential is due to overall the ion interactions together; if there’s NO conductance for an ion, it means the membrane isn’t permeable to it; this ion doesn’t contribute to membrane potential

    • -low conductance: will contribute, but not that much
    • -high conductance: membrane is WIDE open to transport of an ion

    (the ease at which an electric current passes [opposite of resistance]; G=I/V)
  5. to modify the permeability of the membrane:
    you can close or open ion channels

    -opening channels increases conductance (inevitably)
  6. depolarization
    • -happens when you increase membrane permeability to Na+
    • -change in a cell's membrane potential, making it more positive (aka less negative)
  7. hyperpolarization
    • -happens when you increase permeability to K+
    • -a change in a cell's membrane potential that makes it more negative
    • -opposite of depolarization
    • -is often caused by efflux of K+ (a cation) through K+ channels, or influx of Cl– (an anion) through Cl– channels
  8. you can play around with membrane potential without affecting in any way:
    •the concentration of ions on either side of the membrane

    -only thing that matters is the permeability of the membrane to Na & K, (Cl & Ca too) and HOW MUCH they LET ions go through; not how many ions go through
  9. the resting membrane potential is due to:
    • -the selective permeability of the membrane to K+ via potassium channels
    • -BUT significant energy is stored in the Na+ gradient
  10. Free energy change: ΔG
    ΔG = ΔGc + ΔGm

    ΔGc = RT* (ln) [ions out]/[ion in]

    • ΔGm = FE
    • F=faraday constant
    • E=membrane electric potential (usually -70mV)

    -if overall free energy change is NEGative, then there's spontaneous movement of the ion inside the cell

    • -at equilibrium
  11. Analog v. Digital Signal Propagation
    • •ANALOG: found in small animals where signal doesn't have to travel very far
    • -aka graded local potentials
    • -more signal there is, the more a cell will depolarize
    • -analogy = LP (sound fades, progogation of signal decays with distance)

    • •DIGITAL: useful for larger animals
    • -aka action potentials
    • -as you increase the signal, the height of the peaks doesn't increases, the FREQUENCYof the peaks increase
    • -low signal level --- low frequency, HIGH signal ---HIGH frequency
    • -they're either completely there or NOT
    • -analogy = iPod; music is always there

    -ropagation of digital information/signal is more robust than analog signal
  12. analog v. digital: comparison
  13. TTX (tetrodotoxin) & TEA
    TTX: blocks action potentials in nerves by binding to (voltage-gated) sodium channels, preventing nerve cells from firing; lose inward Na+ current --- cannot have action potential (no depolarization

    TEA: blocks action potentials in nerves by binding to (voltage-gated) potassium channels, preventing nerve cells from firing; lose outward K+ current --- no action potential (aka hyperpolarization)
  14. Action Potentials depend on:
    -sequential changes in Na+ and K+ Permeability

    • -rising (ascending) phase of an action potential comes from the opening of Na+ channels
    • -falling phase comes from inactivation of Na+ channels and opening of K+ channels
    • -timing is crucial: Na+ channels must open BEFORE K+ channels
  15. Although sodium flows in the cell during depolarization of an action potential:
    the [Na+] (concentraiton) of sodium inside the cell doesn't SIGNIFCANTLY. CHANGE. Number of ions that migrate in is insignificant (Na/K ATP-pump help equilibriate)

    -action potential is in no way due to a change in CONCENTRATION of Na or K
  16. Voltage-gated channels should be:
    • -highly selective
    • -very fast
    • -voltage sensitive
    • -have a mechanism for rapid inactivation: cannot stay open forever
  17. Channels can be gated by (4):
    • (1) changes in membrane potential: voltage-gated channels
    • e.g. Shaker K+ channel

    • (2) ligand binding: ligand-gated channels
    • e.g. Ach receptor

    • (3) mechanical forces: sensory receptors
    • e.g. mechanosensitivechannels

    • (4) channels can be permanently open
    • e.g. open rectifier K+ channels
  18. I don't know, instead of calclulating it each time just memorize the E's for different ions:
  19. Claude says depolarization happens (spikes) at:
    • •-40 mV; the Na+ channel likes it and opens & the membrane channel is depolarized
  20. voltage-gated ion channels = key to action potential
    • -voltage-gated Na+ channels open when membrane depolarization reaches threshold (~ -40 mV???)
    • -opening of Na+ channels = further depolarization
    • -this makes the Na+ channels open larger
    • -opening of Na+ channels/depolarization = autocatalytic
    • -when Na+ channels are fully opened: membrane potential becomes close to Na+ potential (~ +50mV)

    -voltage-gated K+ channels have the same properties but they lead to negative feedback; their opening leads to repolarization and therefore their own closing
  21. Na+ ions are_______ than K+ ions
    • -Na+ ions are smaller than K+ ions; so how do K+ channels prevent Na+ ions from entering?
    • -the ability to selectively filter comes from backbone carboyl oxygen on residues in the P segement of the channel
    • -as K+ enters the channel, it becomes dehydrated (loses bound water molecules from the extracellular fluid) but they're replaced by binding of the 8 carbonyl oxygens inside the channel [btw, it's easier to remove water molecules from K+ than Na+, b/c it's a larger molecule w/ more layers]

    • -a dehydrated Na+ ion is TOO SMALL to bind all 8 carbonyl oxygens in the channel, therefore they prefer to remain in water in their original conformation
    • -the same is true for Ca2+ ions
  22. the smaller the ion, the ____ energy is takes to REMOVE the water from the ion
    • -the smaller the ion, the MORE energy is takes to REMOVE the water from the ion
    • -in the small ion, the water molecules get closer to the nucleus, making the attraction stronger

    • -K+ ion: 133 Å
    • -Na+ ion size: 95 Å
  23. ball-and-chain mechanism for voltage-gated channels
    • -so the channel opens, changing the inside of the cell from negative to positive
    • -the ball is made up of molecules with lots of positive charge
    • -understanding that most channels are amphipathic (aka hydrophobic when interacting with membrane fats but polar/hydrophilic on the inside of the poor and on the extracellular side), we know the inside of the pore is negative charged
    • -this negatively charged pore attracts the positively charged ball (especially because after depolarization the inside of the cell is now positive) causing it to be blocked from the inside
    • -leads to an inactivated conformation, not closed

    -Na channel deactivates itself using this mechanism; triggered by a strong depolarization

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