Every cell in our body has a cell membrane that separates it from the outer environment of the tissue. The concentration of different ions across the cell membrane is different.

As a result, polarity is established on the two sides of the membrane. This is called membrane potential.

Most of the cells have more negative ions on the inner side of the membrane. Thus, most of the cells have negative membrane potential.

Depolarization is a process by which cells undergo a change in membrane potential. It is a process of shift in electric charge that results in less negative charge inside the cell.

In this article, we will discuss the physiology of depolarization, ion channels that participate in this process and how different cells undergo depolarization. We will also discuss some drugs that can alter the process of depolarization.

Physiology of Depolarization

The process of depolarization is highly dependent on the intrinsic electrical nature of the cells. In order to understand the process of depolarization, we have to understand the concept of resting membrane potential.

Resting membrane potential

When a cell is at rest, the potential across its cell membrane is called resting membrane potential. For most of the cells, the resting membrane potential is negative relative to the outside of the cell.

The process of generation of resting membrane potential involves passive ion channels, ion pumps, and voltage-gated ion channels. Cells use these machines to keep a high concentration of negative ions inside the cells. As a result, negative membrane potential is maintained.

Factors contributing to the resting membrane potential include the following:

Organic Anions

Usually, cells have more abundant organic anions inside the cells such as oxalate ions etc. The negative charge of these negative anions contributes to the resting membrane potential.

K+ Channels

Most of the cells in body have abundant K+ channels in their membranes. In the usual setting, ten times more abundant potassium ions are present inside the cell than in the extracellular space.

These potassium ions have diffusion gradient directed towards the extracellular space. Thus, they continue to diffuse through the open K+ channels and leave the cells. This loss of positively charged ions further contributes to the negative resting membrane potential inside the cell.

Sodium Potassium Pump

Sodium potassium pump contributes a lot to the resting membrane potential. The concentration of sodium ions is more outside the cell than on then inside. On the other hand, the concentration of potassium ions is more on the inside of the cell than the outside.

Thus, the diffusion gradient of sodium is directed towards the inside of the cell and that of potassium is directed towards the outside of the cell.

Sodium potassium pump is an energy-driven pump that uses ATP to pump the sodium and potassium ions against their concentration gradient. For every two potassium ions pumped inside the cell, three sodium ions are pumped outside.

It results in a net loss of positive ions from the cell.

All the above-mentioned factors contribute to the establishment and maintenance of negative membrane potential within the cell.

Process of depolarization

After understanding the concept of resting membrane potential, we will now discuss the process of depolarization.

A cell has the capacity to undergo depolarization after it has established a resting potential. Depolarization causes the rapid change in membrane potential from negative to positive state.

The process of depolarization begins with a stimulus. This stimulus can be a simple touch, light, foreign particle, or even electrical stimulus. This stimulus causes a voltage change in the cell.

This initial voltage change causes the opening of voltage-gated sodium and calcium channels inside the cell membrane. The positively charged ions rush through these channels. As a result, the inside of the cell becomes more positive. The membrane potential changes from negative to positive state.

Depolarization in different cells

The basic principle of depolarization is the same as described under the heading of physiology. However, different cells in the body respond to different stimuli and use different ion channels to undergo the process of depolarization. All this is in coherence with the function of that cell.

We will discuss the process of depolarization in reference to neurons, endothelial cells, and cardiac cells.


Neurons can undergo depolarization in response to a number of stimuli such as heat, chemical, light, electrical or physical stimulus. These stimuli generate a positive potential inside the neurons.

When the positive potential becomes greater than the threshold potential, it causes the opening of sodium channels. The sodium ions rush into the neuron and cause the shift in membrane potential from negative to positive.

Depolarization of a small portion of neuron generates a strong nerve impulse. The nerve impulse travels along the entire length of neuron up to the synaptic terminal.

Once the nerve impulse reaches the synaptic terminal, it causes release of neurotransmitters. These neurotransmitters diffuse across the synaptic cleft. They act as a chemical stimulus for the post-synaptic neuron. These neurotransmitters, in turn, cause the depolarization of postsynaptic neurons.

Endothelial cells

Vascular endothelial cells line the inner surface of blood vessels. These cells have structural capability to withstand the cardiovascular forces. They also play an important role in maintaining the functionality of the cardiovascular system.

These cells use the process of depolarization to alter their structural strength. When the endothelial cells are in a depolarized state, they have marked decreased structural strength and rigidity. In depolarized state, endothelial cells also cause a marked decrease in vascular tone of blood vessels.

Cardiac Cells

Depolarization of cardiac myocytes causes contraction of the cells and thus heart contraction occurs.

Depolarization first begins in the SA node, which is also called the cardiac pacemaker. SA node has automaticity. The resting membrane potential of SA node is less negative than that of other cardiac cells. This causes opening of sodium channels. Sodium ions continue to diffuse into the cells of SA node.

When the membrane potential becomes greater than the threshold potential, it causes the opening of Ca+2 channels. The calcium ions then rush in, causing depolarization.

Beginning in the SA node, the depolarization spreads to atria and through AV node an AV bundle to Purkinje fibers causing depolarization and contraction of ventricles.

Skeletal Muscles

The excitation of skeletal muscle by motor neurons causes the opening of voltage-gated sodium channels. The opening of sodium channels causes depolarization of the skeletal muscle.

The action potential from the motor neuron also travels through the T-tubules. It causes the release of Ca2+ ions from the sarcoplasmic reticulum. Thus, contraction of skeletal muscle occurs. This entire process is also termed as excitation-contraction coupling.  

Drugs that block the process of Depolarization

There are certain drugs that can block the process of depolarization. They cause persistent opening of the ion channels. The positively charged ions continue to diffuse into the cells.

As a result, the cells are unable to recover from the initial period of depolarization. They remain in persistent state of depolarization and do not respond to the stimuli.

These drugs include nicotinic agonists such as suxamethonium and decamethonium.


Depolarization is a process that causes rapid change in membrane potential from negative to positive state.

When a certain stimulus is applied to a cell, it causes an initial voltage change in the cell.

When the threshold potential is reached, it causes the opening of ion channels. As a result, the membrane potential changes from negative to positive state.

In order to undergo depolarization, the cells must establish and maintain a negative resting membrane potential. Factors that play an important role in the establishment of resting membrane potential include:

  • Organic anions
  • K+ channels
  • Sodium potassium pump

The process of depolarization has different consequences in different cells of the body.

In neurons, nerve impulse transmission occurs through the process of depolarization.

In vascular endothelial cells, the process of depolarization helps to regulate the structural rigidity and vascular tone.

In cardiac muscles, depolarization causes contraction of cardiac muscles.

The skeletal muscles also respond to depolarization by contraction.

Nicotinic agonists can cause prolonged depolarization state of the cells. They prevent the cells from undergoing repolarization. As a result, cells do not respond to the new stimuli.


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