Assuming that the resting potential is zero and the other mechanisms were exactly the same, how would it affect the generation of spikes in terms of excitatory and inhibitory postsynaptic potentials(EPSP and IPSP). Trying to understand the reason behind negative resting potential, not how it is maintained, but why so. Does it mean EPSP is inherently suppressed by design?

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    $\begingroup$ Most excitatory synapses have a reversal potential around 0 mV. Since opening a synapse can only bring the cell toward the synapse's reversal potential, EPSPs would have no electrical effect on the cell in this case (although they would still have a chemical effect by allowing ions to flow down their chemical gradients). IPSPs would be much stronger. There is a very interesting question here--why do we go to the effort of hyperpolarizing the membrane at all? Why not simply have excitatory synapses with positive reversal potential (ie, only permeable to sodium or calcium)? $\endgroup$
    – Luke
    Commented Jun 15, 2013 at 11:59

2 Answers 2


There are two very different questions here. The first question is simple (although it could be interpreted a few different ways). The second question is very tricky and I am actually not certain we know the answer.

1. What do PSPs look like if the resting membrane potential is 0 mV?

If a cell is being held at 0 mV, its voltage-gated conductances are essentially broken and it is not actually able to fire an action potential. But let's put that aside and focus on synaptic events. Let's also assume that the reversal potentials for each ion are 'normal'.

The short story is that most excitatory receptors have a reversal potential near 0 mV, so EPSPs would have little direct effect on the membrane potential (remember this rule: current passing through an ion channel can only push the membrane potential toward the reversal potential of that channel). Inhibitory receptors tend to reverse around -75 mV, so they would have a large driving force and would strongly polarize the cell.

The slightly-longer story is that EPSPS would still have some effect--when ion channels open, ions flow in the direction of their electrochemical gradient. For excitatory receptors, this means that sodium flows into the cell, potassium flows out, and calcium flows in. The net electrical current would be roughly zero, but there would be an exchange of ions, and an opportunity for those ions to activate secondary signaling pathways.

Another effect of opening ion channels is a reduction in the resistance of the cell membrane. Thus at 0 mV, excitatory synapses can actually shunt IPSPs.

2. What is the reason for having a negative resting potential at all?

The first thing to recognize is that neurons store a large amount of energy in their chemical gradients. Potassium is pumped into the cell while sodium, chloride, and calcium are pumped out. Running these pumps is metabolically expensive (your brain takes up 20% of your metabolism at rest!), and the chemical energy burned in the process (ATP) becomes potential energy in the chemical gradient. Another way of saying this is that each of these ions prefers to be on the other side of the membrane, but the pumps keep them where they are.

Ions are generally pumped in such a way as to maintain charge balance--for every positive charge pumped in, one positive charge goes out. Now if you happen to have channels that admit only a single type of ion (we do), then opening that channel will result in an immediate flow of ions. But wait! Unlike the pumps, this ion flow is not charge-neutral, so after a very short time, the membrane becomes charged, and that charge imbalance (voltage) counteracts the chemical gradient (if ions dislike being on the wrong side of a chemical gradient, they absolutely hate being on the wrong side of an electrical gradient).

So what we have now is a huge energy store in the form of chemical gradients, and a means for the neuron to rapidly convert that energy into electrical potential. If the neuron wants to depolarize, it needs only open sodium or calcium channels. If it wants to repolarize, it opens potassium or chloride channels. You can think of it like a balloon connected by hose to two tanks: one high pressure, the other a vacuum. Open one valve and the balloon fills, open the other and it empties.

Ok, that was long but I am finally ready to talk about resting potential. The how is easy: neuronal membranes are more permeable to potassium than sodium. One of the valves is always open a little bit, and this drags the membrane potential negative, away from zero. Which is to say that the resting membrane potential is not at all the "driving force" for neuronal activity. Rather, it is almost just a side-effect of the real powerhouse--the chemical gradients.

I mentioned that neurons spend a lot of energy maintaining their chemical gradients. Why then, would the cell allow its potassium gradient to simply leak away? This is not an easy question! The lazy answer is "because all the voltage-sensitive channels operate in the range from -70 to 0 mV". I call this lazy because if there really was no benefit to having the cell rest at -70 mV, then evolution would find a way to conserve all that energy wasted by leaking potassium. So there must be a better reason. I've turned this into its own question here: Why do neurons have a negative resting potential?

  • $\begingroup$ Nice job with it. I think your bio question would have been on topic here as well. If you don't get a response over there (except for some idiot named jonsca commenting ;)) you could flag it to be migrated. $\endgroup$ Commented Jun 16, 2013 at 7:19
  • $\begingroup$ @ChuckSherrington just letting you know that your comment was flagged as "rude/offensive". :-) I think the joke that jonsca and Chuck are the same person may have been missed. $\endgroup$ Commented Jun 17, 2013 at 2:14
  • $\begingroup$ Well I flagged the comment, any reader would have no clue they are the same person. :-| $\endgroup$
    – shrm
    Commented Jun 17, 2013 at 7:54
  • $\begingroup$ @mishr No worries! I think it's funny, as did Jeromy, I think. I hope I won't be suspended :P $\endgroup$ Commented Jun 17, 2013 at 14:24

Potential is relative, so having a negative resting potential simply means that the inside of the cell is negative with respect to the outside.

Since an EPSP is going to be an overall positive change, yes, the negative resting potential does keep the cell at far below the threshold, but recall that over a short time duration, these EPSPs sum up to eventually push the cell above threshold.

A cell with no membrane potential is the equivalent of a dead battery, there is no "electromotive force" (i.e., voltage), so there is no driving force for current changes (except in the case of leak currents due purely to concentration differences). Therefore, there is no calcium ion influx at the presynaptic terminal, no neurotransmitter containing vesicles can bind, and no transmitter is released into the cleft.

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    $\begingroup$ See if your library has the undergrad version of the Kandel book (amazon.com/Essentials-Neural-Science-Behavior-Kandel/dp/…). It's been out of print for about 15 years, but it's absolutely the best explanation of this sort of thing (aside from Kandel, Schwartz, Jessel, et al, itself). $\endgroup$ Commented Jun 12, 2013 at 14:17
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    $\begingroup$ This is a bit misleading--a cell with 0 resting potential is not a 'dead battery'; it can still have chemical gradients and active synapses. I agree that action potentials will not be generated, but inhibitory synapses will still function (at least with spontaneous release) and excitatory synapses will still exchange ions when they are activated and admit calcium into the postsynaptic cell, even if they pass little net current. $\endgroup$
    – Luke
    Commented Jun 15, 2013 at 11:53
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    $\begingroup$ @Luke The calcium channels are (in this case) voltage gated, though. $\endgroup$ Commented Jun 15, 2013 at 14:12
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    $\begingroup$ I understand your point, but I'm speaking about a steady state situation instead of a transient one. $\endgroup$ Commented Jun 15, 2013 at 14:15
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    $\begingroup$ Even in the steady-state case, the statement that "there is no driving force for current changes" is false--there are still competing electrochemical gradients, opening sodium and calcium channels will still depolarize the cell, opening potassium and chloride channels will still hyperpolarize the cell. In fact, if we assume the presynaptic terminal is at 0 mV, then voltage-gated calcium channels will be open, calcium will flow into the terminal, and the synapse may release neurotransmitter even in the absence of action potentials. $\endgroup$
    – Luke
    Commented Jun 15, 2013 at 14:49

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