Is the axon hillock still the place where one thinks and talks of that action potentials are initially created? (I've heard this place moved into the direction of the axon initial segment.)

If one doesn't want to commit oneself whether it's the axon hillock or the initial segment where action potentials are initially created – because it's somewhere inbetween or at both of them, or it depends on the type of neuron, or we don't know, or we don't care:

How does one talk about that place unequivocally?

Is there an abstract (non-anatomical) terminus technicus for "the place where action potentials are initially created"?


1 Answer 1


Action potentials are initiated where there is a high density of voltage-gated $Na^+$ channels and that may vary from cell to cell, as you guessed. For an illustrative example see the figure below, reproduced with permission from Kole et al. (2008).

enter image description here Density of voltage-gated $Na^+$ channels and $Na^+$ influx along the axon of a cortical pyramidal neuron.
Reproduced with permission © Nature Publishing Group

As you can see, in this cell type voltage-gated $Na^+$ channels, labelled in green in the left-most image, are predominantly expressed away from the axon hillock. We can also observe that the expression of voltage-gated $Na^+$ channels correlates with the degree of $Na^+$ influx in a monotonic relationship (right-most panel).

In smaller cells action potential initiation can happen closer to the axon hillock and in cells of some invertebrates even in multiple locations (Kole and Stuart 2012). What may be the advantage of using the axon initial segment (AIS) as the sole site of initiation of action potentials (APs)? Here is a direct quote from Kole and Stuart (2012):

[The AIS] has a small local capacitance ($C$) and therefore requires less inward current ($I$), that is, a smaller number of $Na^+$ channels per unit area, to generate APs compared to larger structures, such as the soma or proximal dendrites. Hence, the AIS is also an energetically favorable site for AP initiation. Furthermore, the small capacitance of the AIS favors rapid changes in membrane potential, as occurs during the upstroke of the AP ($dV/dt = I/C$). Finally, it is worth noting that having a single site of AP generation provides neurons a single locus where inhibition can gate AP initiation. [...] Initiation of APs further from the soma, taking advantage of the electrical isolation of this region, is a strategy used in some neurons to increase their capacity to discriminate the arrival time of different synaptic inputs.

M. H. P. Kole et al., Action potential generation requires a high sodium channel density in the axon initial segment. Nat. Neurosci. 11, 178–186 (2008). doi: 10.1038/nn2040
M. H. P. Kole, G. J. Stuart, Signal Processing in the Axon Initial Segment. Neuron. 73, 235–247 (2012). doi: 10.1016/j.neuron.2012.01.007

  • $\begingroup$ So wouldn't something like "spike-generating density" be a perfect name, analoguous to [postsynaptic density]( google.de/url?sa=t&source=web&rct=j&url=https://…) $\endgroup$ Commented Nov 24, 2017 at 13:25
  • $\begingroup$ I only addressed what I think is the essence of your question, i.e. where are action potentials generated, and avoided the linguistic aspect. Usually, terms are established by use in the literature when there is a purpose for them and it's not my place to create new terms in this forum. Suffice it to say that the phrase predominantly used is "action potential initiation site" or a variant thereof. $\endgroup$
    – vkehayas
    Commented Nov 24, 2017 at 13:39
  • $\begingroup$ That's what I wanted to know! I didn't want to invent a new term, when there is already an established one. $\endgroup$ Commented Nov 24, 2017 at 13:42
  • $\begingroup$ By help of the term you gave me, I immediately found this article: ncbi.nlm.nih.gov/m/pubmed/8786434 $\endgroup$ Commented Nov 24, 2017 at 14:10
  • $\begingroup$ ... and this one about multiple AP initiating sites: ncbi.nlm.nih.gov/m/pubmed/11535672/?i=2&from=/8786434/… $\endgroup$ Commented Nov 24, 2017 at 14:13

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