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I know that many neurons have an input current-spiking frequency (I-F) relationships, e.g. as seen here.

However, all the I-F curves I've encountered show the input current in a fairly small range (few pA or nA), suggesting that there is no limit to this behavior.

However, if the current is increased indefinitely, there is a point where the membrane voltage does not recover to the resting, or smaller, potential. For example, here are voltage traces of a simulated mitral cell:

At 0.1nA:

enter image description here

0.5nA:

enter image description here

1nA:

enter image description here

10nA:

enter image description here

How do neurons limit the amount of current that enters the cell? If the cell is large, with many incoming synapses, it seems like there would be stimuli that could result in "too many channels" open at the same time. How do cells ensure the input current remains within the acceptable range?

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Current is Voltage (driving potential) times conductance. As the membrane potential approaches the Nernst potential of the conductance, the current approaches 0. Conductances can be turned on or off through receptor binding, but there is no such thing as voltage-independent current injection (at least under physiologically relevant conditions).

Indeed, it is the case that if you artificially inject large amplitudes of current into neurons, you observe voltage traces similar to your simulations. This will very quickly lead to cell death.

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  • $\begingroup$ so the current could still be high, but only for a short duration (<1 ms) before the membrane v reaches one of the Nernst potentials? Then the answer is that the Nernst potentials are what keeps the cell within the operating range. $\endgroup$ – Justas Jun 15 '16 at 19:15
  • $\begingroup$ sure, if you want to say it that way $\endgroup$ – honi Jun 15 '16 at 20:32
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    $\begingroup$ good point. In addition, there are homeostatic plasticity mechanisms that seems to control the overall gain if the firing rate is too high or too low. $\endgroup$ – Memming Jun 16 '16 at 13:47

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