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Membrane potential: want to learn more about it?

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Membrane potential

A resting membrane potential is the difference between the electric potential in the intracellular and extracellular matrices of the cell when it isn’t excited. Every cell of the body has its own membrane potential, but only excitable cells - nerves and muscles - are capable to change it and generate an action potential

For this reason, membrane potential for excitable cells when they are not excited is called the resting membrane potential, while its changes are associated with an action potential.

Key facts about the membrane potential
Definition Difference between the electric potential of the cellular membrane matrices when the cell isn’t excited
Factors that determine it Difference between intra- and extracellular ion concentration
Na-K pump
Permeability of the cell membrane for ions

This article is actually Physio 101, and it will discuss the definition of membrane potential, from where it originates, and how its values affect the ability of the cell to generate action potential (impulse).


Resting membrane potential (EM) originates from the different concentrations of ions (expressed in mmol/l) at the inner and outer surface of the cell membrane. There are four excitable tissues in our body, and all of them have different EM values:

The negative values indicate that the cytoplasm is more electronegative than the extracellular space. The values of EM depend on several factors:

  • Concentration of ions inside and outside the cell. Ions that contribute the most are the sodium, potassium, calcium, and chloride ions. 
  • Activity of the sodium-potassium pump.
  • Variable permeability of the cell membrane for ions.


There are many ions in the cell and extracellular space, but not all of them can pass through the cell membrane. Those who can, are called diffusible ions (sodium, potassium, calcium, and chloride), and those who can’t are non-diffusible ions (proteins). Nonetheless, both groups of ions contribute to membrane potential. Why? Ions are chemical elements that carry electricity, some positive (+) and some negative (-). Usually, there are more negative ions inside the cell than outside, which is why the EM has the negative values. This negativity is mostly due to non-diffusible proteins (-).

Diffusible ions are responsible for the change of the membrane potential. During action potential, a redistribution of the ions occurs, where large amounts of sodium (+) enter the cell, making the membrane potential less negative and closer to the threshold for the action potential.

Distribution of ions
Intracellular space Sodium = 14 mmol/l
Potassium = 140 mmol/l
Calcium = 0.0001 mmol/l
Chloride = 5 mmol/l
Extracellular space Sodium = 142 mmol/l
Potassium = 4-5 mmol/l
Calcium = 2.5 mmol/l
Chloride = 103 mmol/l

Sodium-potassium pump (Na-K pump)

Another factor that controls membrane potential is the Na(+)-K(+) pump. This pump uses energy to expel 3 molecules of sodium in exchange for 2 molecules of potassium. This is important because this pump creates concentration gradients for sodium and potassium, allowing more sodium in the extracellular space, and more potassium in the intracellular space. 

Sodium-potassium pump (diagram)

The  concentration gradient will later contribute to generating an action potential, because of one of the laws of physics. By concentration gradient definition, every element modifies its concentration gradient to seek equilibrium. For example, ions will diffuse from a place of higher concentration to a place of lower concentration until the concentration of the element is equal on both sides. This means that the sodium will diffuse from extra- to intracellular space, and the potassium will do the opposite. More about this process can be found in the action potential article.

Cell membrane permeability

The third factor that affects the membrane potential is the permeability of the membrane for the sodium and potassium, which depends on the ion channels. Ion channels are specialized proteins of the cell membrane that enable migration of the ions. There are two types of ion channels:

  • Passive channels – which are the pores within the cell membrane, through which the molecules pass depending on their concentration gradient. 
  • Active channels – which open and allow the ion transport either depending on the change of the membrane potential (potential-gated channels), or after binding of some other protein (ligand-gated channels), or after mechanical stimulation.

Pores contribute to establishing resting membrane potential, and they are found along the entire excitable cell membrane. When the cell isn’t excited, diffusion of ions occurs only through the pores. Note that during rest, a lot more potassium pores are open than for the sodium. For this, the potassium efflux is larger than the sodium influx, which contributes to maintaining the negativity of the intracellular space and EM.

Ligand-gated channels are located near the synapses and are responsible for local hypo- or hyperpolarization of the cell after the neurotransmitter binds to them. Potential-gated channels are responsible for generation and propagation of an action potential, which eventually causes the release of a neurotransmitter. They are found in the membranes of axons and axon terminals. 

Equilibrium potential

From the aspect of concentration gradient, we would expect that all diffusible ions pass through the cell membrane until their concentrations are equal from both sides. But still, that doesn’t happen. Why? There is another physical component in this entire process which opposes to the concentration gradient, called the electric gradient, that works similar to a magnet.

Let’s take potassium as an example. Intracellular concentration of potassium is 140 mmol/l, while the extracellular is 4-5 mmol/l. We would expect that the potassium diffuses outside of the cell until there are around 70 mmol/l of potassium from both sides of the membrane. But, since potassium is a positive ion (+), its efflux increases the positivity of the extracellular space, and increases the negativity of the intracellular space. This leads to the point where the extracellular space is positive enough to repel the potassium, and the intracellular space becomes negative enough to attract the positive potassium. This point is called the electrochemical equilibrium. Physiologists calculated the value of the EM when the potassium cannot diffuse out of the cell anymore, and it is -94 mV. 

Now, let’s look at the sodium, which is also a positive ion. Because of the concentration gradient, the sodium tends to influx into the cell. At some point, the cell becomes electropositive enough to repel the new sodium ions, and thus opposes the sodium concentration gradient, reaching the electrochemical equilibrium. The value of electropositivity that stops the sodium influx is +61 mV.

As we mentioned earlier, potassium diffusion mostly affects the resting membrane potential. On the other hand, the sodium diffusion is massive during an action potential. This implicates two things:

  • Membrane potential cannot be more negative than -94 mV
  • Membrane potential cannot be more positive than +61 mV

Membrane potential: want to learn more about it?

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