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All the living cells are electrically neutral with having an equal number of positive and negative charges. The cells try their best to maintain this electrical neutrality. The cytoplasm of the cells contains different positive and negative species such as inorganic ions, organic ions, acids, proteins, etc. The concentration of all these substances is kept within a narrow range that is necessary for the normal functioning of the cell.

Although the cells are neutral, there exists a difference in the concentration of charges on the inner and outer sides of the cells. This difference in charges creates a potential difference across the membrane called the membrane potential. Some electrical potential exists across all types of cells present in the human body.

An effort to change the membrane potential so that charges on both sides of the cell become equal and similar is called depolarization. Because of the membrane potential, two electrical poles exits across the plasma membrane. Depolarization is the process by which potential difference is brought to zero by allowing certain ions to diffuse through the membrane. The depolarization process is carried out by different means in different cells of the body.

In this article, we will talk about membrane potentials, resting membrane potential, the general principle of depolarization, and the various ways of depolarization in different cells of the body.

Membrane Potential

As stated earlier, a potential difference exists across the plasma membrane of all the cells present in our body. The most important reason for this potential difference is the selective permeability of plasma membranes. These membranes allow only certain substances to pass into or out of the cell.

Let us take an example of the human body. The potassium ions are present in higher concentrations within the cytoplasm as compared to the extracellular fluid. On the other hand, the concentration of sodium ions is higher in the extracellular fluid with respect to the cytoplasm of the cells.

The plasma membranes in the human cells have certain potassium channels. The potassium ions can easily diffuse across the plasma membrane down the concentration gradient. These ions continue to diffuse into the extracellular fluid and create an electronegativity inside the cells. The inside of the membrane becomes negative with respect to the outside of the cells due to the loss of positive charges.

Although the sodium ions are in higher concentrations outside the cell and they must diffuse into the cytoplasm, they don’t do so. It is because the cell membrane is not permeable to sodium ions. So, these ions remain outside the cell, further increasing the electropositivity of the extracellular fluid.

In this way, the membrane potentials are generated due to the selective permeability of the plasma membrane to certain ions.

Resting Membrane Potential

The potential difference across the plasma membrane of a cell when it is in a resting state is called the resting membrane potential. Almost all the cells in the human body have a negative resting membrane potential as compared to the extracellular fluid.

The depolarization process tends to change this resting membrane potential when the cell is stimulated. In order to understand the depolarization process, it is important to have an idea of factors contributing to the resting membrane potential.

The resting membrane potential of a non-conducting neuron (when it is not active) is -90 millivolt. It means that the inside of the neuron has 90 millivolts more negative potential as compared to the extracellular matrix. The resting membrane potential of skeletal muscle cells is around -95 millivolt and that of smooth muscles is around -60 millivolt.

The following are the major factors that contribute to the resting membrane potential in the neurons and other cells of the body.

Efflux of Potassium Ions

The concentration of potassium ions inside the cells is higher than the extracellular fluid. The plasma membrane is also permeable to potassium ions due to the presence of potassium ion channels.

Thus, the potassium ions diffuse out of the cell down their concentration gradient. The loss of potassium ions from the cell contributes to a net electronegativity in the cell. In this way, the efflux of potassium ions plays a role in generating resting membrane potential.

Contribution of Sodium ions

Recall that the concentration of sodium ions inside the cells is less than that in the extracellular fluid. The plasma membrane of cells in the resting state is impermeable to sodium ions. These ions cannot cross under normal conditions.

However, a small number of sodium ions may cross the plasm membrane through sodium-potassium leak channels. These ions move down the concentration gradient from the extracellular fluid into the cytoplasm. The influx of sodium ions contributes to increasing the negativity inside the cell.

As only a small number of sodium ions can diffuse inside, their contribution to resting membrane potential is very low. They only make it a little less negative than what it should be as predicted by the efflux of potassium ions.

Role of Sodium Potassium Pump

The sodium-potassium pump is a protein channel located in the plasma membranes that tend to pump ions against their concentration gradient. It does so by using energy in the form of ATP.

The sodium and potassium ions are being moved against their concentration gradient. The sodium ions are pumped out of the cell while the potassium ions are pumped towards the cytoplasm.

In one cycle, it pumps two potassium ions inside the cells and three sodium ions into the extracellular fluid. Thus, with each cycle, one positive ion is lost from the cell that results in electronegativity inside the cells. This loss of positive ions contributes to the negative resting membrane potential.

The sodium-potassium pump uses one ATP molecule in one cycle. The ATP is cleaved to ADP and inorganic phosphate and the released energy is used to pump ions.

Organic ions

The cytoplasm of the cell is rich in organic ions that contribute to the resting membrane potential. Most of the organic ions carry a negative charge. These ions cannot leave the cell as the plasma membrane is impermeable to these large molecules.

These large organic negative ions are trapped inside the cell and thus contribute to the negative resting membrane potential. examples of such ions include acetate ions, oxalates, and proteins, etc.

Depolarization Process

After understanding the basic concept of membrane potentials and resting membrane potential, let us now move our discussion to the process of depolarization. Depolarization results in changing the membrane potential from negative to zero or positive.

The process of depolarization begins only when a cell is excited. The excitation of the cell starts certain processes that change the state of membrane potential. The new membrane potential thus generated is called an action potential. Thus, depolarization involves two steps;

  • Stimulation of the cell
  • Development of an action potential

Both of these steps are discussed below.

Stimulation of the cell

When a cell is inactive or at rest, it maintains the resting membrane potential across the plasma membrane. The depolarization only begins when the cell is stimulated to be active. It can occur via various environmental stimuli.

The different stimuli are detected by the receptors present on the cells. These receptors then cause changes in the membrane permeability resulting in an action potential.

Different types of stimuli that can begin the process of depolarization are as follows:

  • Light stimulus as in rods and cons
  • Pain stimulus in skin
  • Touch, pressure or vibration stimulus
  • Heat or cold stimulus

Some cells do not need an environmental stimulus and can be activated by some molecular stimuli such as hormones or neurotransmitters. It is seen in the case of cells involved in coordination, intrabody signaling, and performing actions ordered by the control systems of our body. For example, skeletal muscles undergo depolarization when they are excited by the neurotransmitters released at the motor endplate.

Some cells do not need any external stimulus and can undergo

Generation of an Action Potential

The stimulation of a cell causes changes in the selective permeability of the plasma membrane. The diffusion of ions across the membrane is affected. It disturbs the distribution of ions in the cell as well as in the extracellular fluid. As a result, the membrane potential changes because of depolarization.

The generation of action potential involves two steps; depolarization and repolarization.


Before stimulation, the cell is in a resting state with the resting membrane potential of around -90 millivolts. When it is excited or stimulated, membrane permeability is changed. The positive ions such as sodium ions begin to diffuse into the cell. These ions tend to rise the potential toward zero. As a result, the new membrane potential is generated called the receptor potential or excitation potential.

Cells have a certain potential limit at which the sodium channels open while the potassium channels are closed. It is called threshold potential and is defined as the potential that must be reached to generate an action potential in the cell.

If the receptor potential is greater than the threshold potential, the efflux of potassium ions stop. Moreover, sodium ions begin to diffuse into the cells via voltage-gated sodium channels. These channels are only opened when the membrane potential becomes greater than a certain value.

Both of these processes result in a net gain in positive ions inside the cell. Eventually, the inside of the cell becomes more positive and the negative membrane potential changes into a positive one.

In this way, the depolarization is completed as the two poles on the sides of the membrane are neutralized.


The depolarization is a momentary change that lasts for only a few milliseconds. Soon after it is over, the negative resting membrane potential is restored by a process called repolarization.

The sodium channels are opened only for a very small fraction of a second. They close soon they are opened. Once the sodium channels are closed, the influx of sodium ions into the cell stops.

In the meantime, the potassium channels are opened again. The potassium ions begin to leave the cell so that a negative potential is created inside the cell.

The sodium-potassium pump also resumes pumping sodium ions out of the cell.

All these processes result in a net loss of positive ions from the cell and the negative resting membrane potential is restored.

Let us now understand how depolarization takes place in different types of cells present in the human body.

Depolarization in Neurons

Neurons are the cells that are responsible for nervous coordination. They conduct nervous impulses in the form of action potentials. An action potential is generated in the neurons when they undergo depolarization.

The process of depolarization in the neurons is the same as described previously. When they are aroused by a stimulus, a receptor potential is generated. If the receptor potential is greater than the threshold potential, the sodium channels open up and depolarization takes place due to the influx of the sodium ions.

Neurons can be stimulated to undergo depolarization in two ways:

  • They can be excited by some environmental stimuli. It happens when the nerve endings act as some receptors such as touch receptors, pain receptors, etc. The environmental stimulus changes the orientation of fiber that causes depolarization.
  • They can also be excited by a neurotransmitter. It happens in the case of neurons that are a part of a synapse. The neurotransmitter released by the presynaptic neuron passes through the cleft and binds to the receptors on the post-synaptic neuron. Here, the receptors are coupled with the sodium ion channels. Activation of these receptors causes the opening of sodium channels that cause depolarization.

Depolarization in Skeletal Muscles

The contraction of skeletal muscles is coupled with the depolarization of muscle fibers. The phenomenon by which the two mechanisms are coupled is called excitation-contraction coupling.

The skeletal muscle fibers are excited by the motor nerve fibers. The axons of motor neurons make synapse with the skeletal muscle fibers at the motor endplate. When an action potential reaches this synapse, the axon of motor neurons releases neurotransmitters. These neurotransmitters activate the receptors on the skeletal muscle fibers that cause the opening of sodium channels. The sodium ions diffuse into the muscle fiber and cause depolarization.

This depolarization is carried by the T-tubules to the sarcoplasmic reticulum where the calcium channels are opened. The calcium ions released from the sarcoplasmic reticulum initiate the process of contraction. In this way, the depolarization and contraction of skeletal muscles are interconnected.

Depolarization in Smooth Muscles

Smooth muscles are the involuntary muscles found in the visceral organs. The contraction of these muscles is also coupled with their depolarization. The smooth muscle cells are innervated by the autonomic nerve fibers. Thus, their contraction and depolarization mechanisms are slightly different than the skeletal muscles.

The resting membrane potential of smooth muscles is -60 to -50 millivolt i.e. less negative than the skeletal muscle fibers. They are not innervated by the motor endplates. Rather, the autonomic nerve fibers make diffuse junctions with the smooth muscle cells. These diffuse junctions release neurotransmitters that diffuse and bind to the receptors on the smooth muscle cells.

The activation of receptors causes the opening of ion channels. The sodium ions contribute very little to the depolarization of smooth muscles. On the other hand, calcium ions are majorly involved in smooth muscle depolarization.

The calcium ion channels are opened by the activation of receptors. Once the ion channels are opened, the calcium ions diffuse into the smooth muscle cells from the extracellular fluid.

The calcium channels are very slow. The open slowly and remain open for more time as compared to the sodium channels. Thus, the depolarization in smooth muscles has more duration than the skeletal muscles.

The calcium ions diffusing into the cell during depolarization are necessary for the contraction to occur. In this way, the contraction and depolarization are coupled.

Depolarization in SA node

The SA node is the cardiac pacemaker. These specialized cardiac cells can undergo depolarization even in the absence of any stimulus. It is due to the automaticity of these cells.

The resting membrane potential of SA node cells is -60 millivolts. These cells have leaky sodium channels that remain open even in the absence of a stimulus. The sodium ions diffuse into the cell via these channels and cause depolarization to some extent.

The threshold for depolarization in the case of SA nodal cells is -40 millivolts. When the threshold potential is reached, the calcium channels are opened and the membrane potential rapidly increases towards zero. It is due to the influx of calcium ions.

Thus, calcium ions are responsible for depolarization of the SA node.

However, calcium channels do not remain open for a long time. They soon close and the calcium influx stops. The potassium channels are then opened to cause repolarization by efflux of the potassium ions.

Once the resting membrane potential is restored, the leaky sodium channels continue to operate. Thus, the SA node continues to undergo the cycle of depolarization and repolarization without a break. The action potential thus generated causes contraction of the cardiac muscle and regulates their rhythm.

Depolarization in Cardiac Muscles

Like skeletal and smooth muscles, the depolarization in cardiac muscles is also coupled with their contraction. These muscles are excited by the action potential traveling in the conductive system of the heart.

The cardiac muscles are connected to each other as well as the cells of the heart’s conductive system via gap junctions. These gap junctions serve as electrical synapses allowing the ions to easily flow between the cells.

When these muscles are excited, sodium channels are opened. The influx of sodium ions into the cells causes depolarization spike in these muscles. Once the spike is over, the potassium channels are opened. In the meantime, the calcium channels also open, resulting in the plateau phase of depolarization. This phase is over when the calcium channels close.

Thus, in the case of cardiac muscle, depolarization is caused by the influx of sodium as well as calcium ions. The calcium ions flowing into the cell during the plateau stage are required for the contraction process. In addition, depolarization of the cell also releases calcium ions from the sarcoplasmic reticulum. These calcium ions are also needed for the contraction of cardiac muscles.


  • Depolarization is the process by which the electrical potentials on both sides of the plasma membrane are neutralized.
  • A potential difference exists across the plasma membrane due to selective permeability. The membrane potential when the cell is at rest is called the resting membrane potential. The factors that contribute to the resting membrane potential are:
    • Efflux of potassium ions
    • Presence of inorganic ions in the cytoplasm
    • Influx of small amount of sodium ions
    • Sodium-potassium pump
  • Most of the cells in a resting state have more negativity on the inside as compared to the extracellular fluid. So, the resting membrane potential is negative.
  • The membrane potential is neutralized in the process of depolarization. It involves the excitation of the cell and the generation of an action potential.
  • Cells can be excited by an environmental stimulus, a chemical messenger, or via the flow of the ions. Some cells can undergo depolarization in the absence of any stimulus.
  • The generation of action potential involves the influx of positively charged ions (sodium or calcium) via open channels.
  • Depolarization of neurons occurs via the opening of the sodium channels.
  • Depolarization of skeletal muscles also occurs via the influx of sodium ions.
  • The depolarization of smooth muscles is due to calcium channels.
  • Cardiac muscles undergo depolarization due to sodium as well as calcium ions influx.
  • The cells in the SA node reach threshold potential via the influx of sodium ions, while they undergo depolarization via calcium ions influx.
  • The contraction of muscles is coupled with their depolarization.


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