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Jan 26 2012

Membrane Physiology Quiz: Inhibitory Synapses

The driving force on a permeant ion–and hence the direction in which it flows when a conduction pathway for it opens–is determined *both* by its concentration gradient *and* by the voltage across the membrane (i.e., the electrical gradient). The membrane potential at which there is no net inward or outward flux for a permeant ion with a given internal and external concentration–i.e., where the chemical potential energy and and electical potential energy of the ion are equal and opposite–is the Nernst equilibrium potential.

Whether an ion flows in or out of the cell depends on the relationship between the Nernst equilibrium potential for that ion and the membrane potential. Unlike sodium and potassium–which must be regulated with very narrow concentration ranges both inside and outside the cell or else shitte goes to hell in a handbasket–cells have the ability to regulate internal chloride concentration within a pretty wide range. Thus, depending on the neuron and its physiological state, the chloride reversal potential can vary for an adult neuron between -40 and -70 mV.

If a neuron with a chloride reversal potential of -50mV is sitting at a membrane potential of -60mV when a chloride conductance is activated, chloride flows *out* of the cell and depolarizes the membrane. However, despite this channel opening event depolarizing the membrane, it can be inhibitory–i.e., it can make the cell less likely to fire an action potential.

Now see if you can figure out why this depolarizing conductance can be inhibitory!

14 comments

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  1. 1
    PZ Myers

    Because it clamps the membrane potential at a level below the threshold to generate an action potential.

    Are there prizes?

  2. 2
    ABradford

    I know I’m not the first to answer, but I needed the thought exercise. This is the sort of thing my PI is always asking at lab meetings.

    Though this is a depolarization, the equilibrium will be -50mV, so it won’t get much closer to the threshold for action potentials than that; the chloride will start to go back in if it does. If these chloride channels are active when excitatory channels open, chloride will still drive the membrane potential towards -50mV from more positive values. So, the more active the chloride channels, the more active excitatory channels have to be to cause an action potential, as they’re pulling against chloride’s equilibrium.

  3. 3
    Comradde PhysioProffe

    These are very good answers, but a complete answer would also refer to the effect of the opening of the chloride channels on a membrane parameter other than the membrane potential.

  4. 4
    NeuroNerd

    oh oh, pick me!

    Shunting! Reducing the membrane resistance so that more depolarizing current has to be injected to change the membrane potential (voltage) by the same amount than otherwise would be needed. So, even though the membrane potential is depolarized, it’ll take more “work” to get the membrane potential to move beyond that than you would need if the chloride channels hadn’t opened! It’s kinda like short-circuiting the excitatory inputs.

    Is that what you were looking for? If not, my grad PI would disown me…

  5. 5
    Sxydocma1

    Where’s Hille when I need him? My answer is forthcoming.

  6. 6
    blindrobin

    And here I though that it was because the membrane was a libertarian membrane and allowed the chloride to reach it’s own potential by making rational choices relative to it’s self perceived well being. Fuckitol !

  7. 7
    anon

    I think NeuroNerd has it right. V=IR. If resistance is reduced by an open channel, the neuron would be less responsive to other inputs.

  8. 8
    Rod

    Wouldn’t chloride ion moving out of the cell essentially neutralize some of the sodium gradient that is needed for rapid influx of sodium and triggering of the action potential?

  9. 9
    Comradde PhysioProffe

    Reducing the membrane resistance so that more depolarizing current has to be injected to change the membrane potential (voltage) by the same amount than otherwise would be needed.

    Correct!

    Wouldn’t chloride ion moving out of the cell essentially neutralize some of the sodium gradient that is needed for rapid influx of sodium and triggering of the action potential?

    Woefully incorrect!

  10. 10
    Namnezia

    I’ve explained this to my undergrads about a million times in class, only about 1/2 of them get it in the first go round. One of them pointed out that IF a depolarizing Cl- current preceded a current mediated by, say a glutamate receptor, then the added depolarization might make it easier for the excitatory current to bring the membrane to threshold if the GABAR have already closed. So in essence it is excitatory.

  11. 11
    tideliar

    Damn I miss this shite

  12. 12
    David

    A shift in the chloride reversing potential is found in some epileptic neurons in human brain. There are ongoing trials of bumetanide both to block seizures and, in infants (the immature neuron has a different reversing potential compared to the mature state), to alter the development of epilepsy. See the article in this month’s Epilepsia by Ben-Ari.

  13. 13
    Isis the Scientist

    Fuck the brain.

  14. 14
    Lacy

    Great one post. Typical trouble is actually G. change ones own thoughts far too repeatedly.

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