<p>In principle, no. An <strong><a href="http://webspace.ship.edu/cgboer/actionpot.html" rel="nofollow noreferrer">action potential</a></strong> is initiated due to the activation of Na<sup>+</sup> channels. These are so-called <strong><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230911/" rel="nofollow noreferrer">voltage-gated channels</a></strong>, meaning that they sense a <strong><a href="https://en.wikipedia.org/wiki/Depolarization" rel="nofollow noreferrer">depolarization</a></strong> and subsequently open their Na<sup>+</sup> pore to allow Na<sup>+</sup> to flow in, further depolarizing the cell. This is the depolarizing phase of an action potential. </p>

<p><strong><a href="https://en.m.wikipedia.org/wiki/Voltage-gated_potassium_channel" rel="nofollow noreferrer">Voltage-gated K<sup>+</sup> channels</a></strong> open up also due to depolarization, but have slower kinetics and hence they kick in later than the Na<sup>+</sup> channels. Influx of K<sup>+</sup> opposes the effect of Na<sup>+</sup> influx and brings the cell membrane potential back to its resting state (or even hyperpolarizes the cell). This ends the action potential (Fig. 1).</p>

<p><a href="https://i.sstatic.net/dUxvW.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/dUxvW.png" alt="AP"></a><br>
<sup>Fig. 1. Action potential and membrane conductances. source: <a href="http://antranik.org/what-is-an-action-potential-nerve-impulse/" rel="nofollow noreferrer">Antranik</a></sup></p>

<p>An action potential cannot be generated in a <strong><a href="https://en.wikipedia.org/wiki/Hyperpolarization_(biology)" rel="nofollow noreferrer">hyperpolarized</a></strong> state, because the Na<sup>+</sup> channels are closed. A depolarization is necessary to open them.</p>

<p>If a neuron was able to fire when hyperpolarized, there would be no regulatory mechanism to inhibit the cell. This would mean it would keep on firing, regardless of its input - not very useful.</p>

<p><sub><strong>Reference</strong><br>
<strong>-</strong> <a href="http://www.ncbi.nlm.nih.gov/books/NBK21668/" rel="nofollow noreferrer">Lodish , The Action Potential and Conduction of Electric Impulses. In: <em>Molecular Cell Biology</em>, 4<sup>th</sup> ed. New York: W. H. Freeman (2000)</a></sub> </p>

CC BY-SA 3.0
2018-01-20T01:38:33.407Z
several neurons have been found that _do_ exhibit action potentials when hyper polarized, and my answer highlights several of these regimes.
Josh.F
CC BY-SA 3.0
2016-06-17T11:16:48.170Z
2016-07-27T21:49:47.120Z
2016-07-27T21:49:47.120Z
AliceD
<p>So far, we're still missing some interesting cases in your answers. Izhikevich has developed a strikingly simple model that covers the following, including several inhibition-induced action potentials, and there are specific cells that have been discovered matching these behaviors:</p>

<p><a href="https://i.sstatic.net/KkOYR.gif" rel="nofollow noreferrer"><img src="https://i.sstatic.net/KkOYR.gif" alt="http://www.izhikevich.org/publications/figure1.gif"></a></p>

<p>(taken from: <a href="http://www.izhikevich.org/publications/whichmod.htm#izhikevich" rel="nofollow noreferrer">http://www.izhikevich.org/publications/whichmod.htm#izhikevich</a>)</p>

<p>Notice:</p>

<ul>
<li><p>M) Rebound spike (as has been mentioned)</p></li>
<li><p>N) Rebound bursting</p></li>
<li><p>O) Threshold variability</p></li>
<li><p>S) Inhibition-induced spiking</p></li>
<li><p>T) Inhibition-induced bursting</p></li>
</ul>

<p>Also Noteworthy:</p>

<ul>
<li><p>K) Resonators, if I recall, can be frequency responsive to inhibitory signals</p></li>
<li><p>P) Bistable, again, if I recall, bistable neurons can be switched with inhibitory signals</p></li>
</ul>

<p>His textbook <em>Dynamical Systems in Neuroscience</em> (and I'm sure several papers, or references) goes through the names of specific cells, for these, such as: Stellate Cells of Entorhinal Cortex exhibit rebound spikes and Spiny Projection Neurons of Neostriatum exhibit bistability.</p>

CC BY-SA 3.0
2018-01-20T01:33:59.280Z
2018-01-20T01:33:59.280Z
Josh.F
<p>Perhaps this is not what you asked, but there's a phenomenon called <strong>rebound spiking</strong> or <strong>postinhibitory spiking</strong> where a hyperpolarization causes spiking. This is due to the oscillatory property of membrane dynamics (certain subsets of type-II neurons). Spikes can be evoked after inhibitory current stops. Figure 7.29 from Izhikevich's book:</p>

<p><a href="https://i.sstatic.net/smdIb.png" rel="noreferrer"><img src="https://i.sstatic.net/smdIb.png" alt="enter image description here"></a></p>

<p>Here's a partial figure from Hasselmo 2014 (recordings from entorhinal cortex stellate cells).</p>

<p><a href="https://i.sstatic.net/k1h7o.jpg" rel="noreferrer"><img src="https://i.sstatic.net/k1h7o.jpg" alt="enter image description here"></a></p>

<p>References:</p>

<ul>
<li><p>Hasselmo, M. E. (2014). <a href="http://dx.doi.org/10.1098/rstb.2012.0523" rel="noreferrer">Neuronal rebound spiking, resonance frequency and theta cycle skipping may contribute to grid cell firing in medial entorhinal cortex</a>. Phil. Trans. R. Soc. B, 369(1635):20120523+.</p></li>
<li><p>Izhikevich, E. M. (2007). Dynamical systems in neuroscience : the geometry of excitability and bursting. Computational neuroscience. MIT Press.</p></li>
</ul>

CC BY-SA 3.0
2016-06-18T11:01:54.147Z
2016-06-18T14:11:44.270Z
2016-06-18T14:11:44.270Z
Memming
<p>Is there any chance that a neuron could fire when hyperpolarized? In that case, would the spike be different than usual?</p>

<neuroscience><neurophysiology>
Can a hyperpolarized neuron fire action potentials?
alagris
# Can a hyperpolarized neuron fire action potentials?

(Asked by: username_0 on 2016-04-25)

Is there any chance that a neuron could fire when hyperpolarized? In that case, would the spike be different than usual?

**Tags:** neuroscience, neurophysiology


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## 3 answers

### Answer by username_3 on 2016-06-18. Score: 5 | Accepted answer

Perhaps this is not what you asked, but there's a phenomenon called **rebound spiking** or **postinhibitory spiking** where a hyperpolarization causes spiking. This is due to the oscillatory property of membrane dynamics (certain subsets of type-II neurons). Spikes can be evoked after inhibitory current stops. Figure 7.29 from Izhikevich's book:

[![enter image description here](https://i.sstatic.net/smdIb.png)](https://i.sstatic.net/smdIb.png)

Here's a partial figure from Hasselmo 2014 (recordings from entorhinal cortex stellate cells).

[![enter image description here](https://i.sstatic.net/k1h7o.jpg)](https://i.sstatic.net/k1h7o.jpg)

References:

* Hasselmo, M. E. (2014). [Neuronal rebound spiking, resonance frequency and theta cycle skipping may contribute to grid cell firing in medial entorhinal cortex](http://dx.doi.org/10.1098/rstb.2012.0523). Phil. Trans. R. Soc. B, 369(1635):20120523+.
* Izhikevich, E. M. (2007). Dynamical systems in neuroscience : the geometry of excitability and bursting. Computational neuroscience. MIT Press.


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### Answer by username_1 on 2016-06-17. Score: 4

In principle, no. An **[action potential](http://webspace.ship.edu/cgboer/actionpot.html)** is initiated due to the activation of Na+ channels. These are so-called **[voltage-gated channels](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230911/)**, meaning that they sense a **[depolarization](https://en.wikipedia.org/wiki/Depolarization)** and subsequently open their Na+ pore to allow Na+ to flow in, further depolarizing the cell. This is the depolarizing phase of an action potential.

**[Voltage-gated K+ channels](https://en.m.wikipedia.org/wiki/Voltage-gated_potassium_channel)** open up also due to depolarization, but have slower kinetics and hence they kick in later than the Na+ channels. Influx of K+ opposes the effect of Na+ influx and brings the cell membrane potential back to its resting state (or even hyperpolarizes the cell). This ends the action potential (Fig. 1).

[![AP](https://i.sstatic.net/dUxvW.png)](https://i.sstatic.net/dUxvW.png)  
Fig. 1. Action potential and membrane conductances. source: [Antranik](http://antranik.org/what-is-an-action-potential-nerve-impulse/)

An action potential cannot be generated in a **[hyperpolarized](https://en.wikipedia.org/wiki/Hyperpolarization_(biology))** state, because the Na+ channels are closed. A depolarization is necessary to open them.

If a neuron was able to fire when hyperpolarized, there would be no regulatory mechanism to inhibit the cell. This would mean it would keep on firing, regardless of its input - not very useful.

**Reference**  
**-** [Lodish , The Action Potential and Conduction of Electric Impulses. In: *Molecular Cell Biology*, 4th ed. New York: W. H. Freeman (2000)](http://www.ncbi.nlm.nih.gov/books/NBK21668/)

> **Comments:**
> **username_2**: several neurons have been found that _do_ exhibit action potentials when hyper polarized, and my answer highlights several of these regimes.  

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### Answer by username_2 on 2018-01-20. Score: 1

So far, we're still missing some interesting cases in your answers. Izhikevich has developed a strikingly simple model that covers the following, including several inhibition-induced action potentials, and there are specific cells that have been discovered matching these behaviors:

[![http://www.izhikevich.org/publications/figure1.gif](https://i.sstatic.net/KkOYR.gif)](https://i.sstatic.net/KkOYR.gif)

(taken from: <http://www.izhikevich.org/publications/whichmod.htm#izhikevich>)

Notice:

* M) Rebound spike (as has been mentioned)
* N) Rebound bursting
* O) Threshold variability
* S) Inhibition-induced spiking
* T) Inhibition-induced bursting

Also Noteworthy:

* K) Resonators, if I recall, can be frequency responsive to inhibitory signals
* P) Bistable, again, if I recall, bistable neurons can be switched with inhibitory signals

His textbook *Dynamical Systems in Neuroscience* (and I'm sure several papers, or references) goes through the names of specific cells, for these, such as: Stellate Cells of Entorhinal Cortex exhibit rebound spikes and Spiny Projection Neurons of Neostriatum exhibit bistability.


---

