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Physiology · General properties, membrane potentials, laws of stimulation, excitability, and inhibition

Resting membrane potential

Resting membrane potential

Resting membrane potential (RMP) is the electrical potential difference between the inner and outer surfaces of the cell membrane in a state of functional rest. In excitable cells, the inner side of the membrane is negatively charged and the outer side is positively charged, which is a key condition for the generation of excitation.

RMP valueVaries from −50 to −100 mV, depending on the number of potassium pores and the activity of ATPases.
Engine of the processThe sodium-potassium pump, which consumes ATP energy to move ions against their gradient.
Potassium insideThe concentration of K⁺ ions in the cytoplasm is 20–30 times higher than their amount in the extracellular environment.
Sodium outsideThe concentration of Na⁺ ions outside is 10–15 times higher than inside the cell.
5 min readFor medical studentsUpdated 09/24/2026
Material prepared by WhiteCoat Pro editorial team based on platform study guidesReviewed by medical editor: Aulov A. A., general practitioner · 09/24/2026

Tissue classification and the concept of polarization

All body tissues are divided into two large groups based on their response to stimulation:

  • Non-excitable tissues: bone, connective, and epithelial.
  • Excitable tissues: nervous and muscular. Their main property is that when exposed to a stimulus, they generate excitation capable of propagating from the point of origin.

For a cell to respond to a stimulus, its membrane must be polarized at rest. This implies a strict charge distribution: the inner surface bears a negative charge (–) and the outer surface bears a positive charge (+).

Ionic asymmetry and active transport

Polarization does not occur on its own. Its foundation is the uneven distribution of ions on both sides of the cell membrane, created by the membrane enzyme $Na^+, K^+$-ATPase (sodium-potassium pump).

Using the energy of ATP hydrolysis, this pump performs active ion transport strictly against their concentration gradient:

  • Potassium ($K^+$) ions are pumped into the cytoplasm. As a result, their concentration becomes 20–30 times higher inside, where they bind to negatively charged cytoplasmic proteins.
  • Sodium ($Na^+$) ions are pumped out. Their concentration in the extracellular fluid becomes 10–15 times higher than the intracellular concentration.

In addition, due to the activity of other membrane enzymes, a high concentration of calcium ($Ca^{2+}$) and magnesium ($Mg^{2+}$) is maintained outside—they are 20–30 times more abundant than inside. Chlorine ($Cl^-$) is 15–25 times more abundant outside, which is necessary to balance the positive charge of the cations accumulated there.

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Stages of membrane potential formation

In the formation of the membrane electrical charge, the main role is assigned to $Na^+$ and $K^+$ ions. The process of spontaneous polarization can be divided into logical stages:

  1. Sodium blockade. The $Na^+$ ions accumulated outside tend to enter the cell along their concentration gradient. However, at rest, the membrane is completely impermeable to them, so the high sodium concentration is reliably maintained in the extracellular environment.
  2. Potassium diffusion. Unlike sodium, the membrane is partially permeable to $K^+$ ions. Through membrane proteins forming leak channels, potassium begins to passively exit the cell outward along its concentration gradient.
  3. Electrostatic interaction. The exited $K^+$ ions cannot go far. Large protein anions ($A^-$) remain inside the cell. They are negatively charged and, due to their large size, cannot pass through the membrane. These anions electrostatically attract positive potassium, holding it near the outer surface. As a result, less than 1% of potassium ions leave the cell.
  4. Potassium equilibrium. A dynamic equilibrium of two forces is formed: the concentration gradient pushes $K^+$ outward, while electrostatic attraction pulls it inward. This is how the potassium equilibrium potential—the main cause of polarization—arises.
  5. Final correction. Chloride ($Cl^-$) ions passively redistribute following the electric field. At the same time, there are minor leak currents—a weak passive influx of $Na^+$ and $Cl^-$ into the cell. This process slightly shifts the final value of the membrane potential from the pure potassium value, making it slightly less negative.

Recording of the resting potential

To measure the membrane potential, a method using glass microelectrodes is used. These are the finest micropipettes filled with electrolyte, whose tip is so small that it is introduced directly into the cell without destroying its membrane.

The device records the electrical potential difference between two points:

  • With a microelectrode inside the cytoplasm (where the charge is negative).
  • With a macroelectrode on the outer surface of the cell (where the charge is positive).

In physiology, it is customary to analyze all changes in membrane potential relative specifically to the inner surface. The magnitude of the potential varies in different tissues and ranges from −50 to −100 mV. This difference is explained by two factors: the varying activity of cellular ATPases and the unequal number of $K^+$ ion leak pores in different types of excitable cells.

Briefly: answers to topical questions

How does the Goldman-Hodgkin-Katz equation explain the final resting potential value?

The Goldman-Hodgkin-Katz equation explains the final resting potential value by taking into account the permeability of the cell membrane to several types of ions simultaneously. Potassium movement depends on the concentration gradient and the electrical potential difference, but the membrane is also permeable to other electrolytes. This formula makes it possible to calculate the actual membrane potential, since chloride ions, in particular, are involved in the process and make an additional contribution to the formation of cytoplasmic electronegativity at rest.

What specific types of ion channels provide potassium diffusion at rest?

Potassium diffusion in a state of functional rest is provided by specialized leak channels.

  • Potassium leak channels are permanently open protein structures through which ions passively exit the cell into the extracellular space along the concentration gradient.

At rest, the voltage-dependent gates of potassium voltage-gated channels are closed, so ion movement is carried out exclusively through leak channels formed by membrane proteins in the shape of a tubule.

How to memorize

Sodium-potassium pump: "Sodium — Out, Potassium — In". This simple rule helps not to confuse the direction of active ion transport.

Class and exam questions

Which ions make the main contribution to the creation of the resting potential?

Potassium ($K^+$) ions play the main role. It is their passive exit from the cell along the concentration gradient and subsequent electrostatic attraction that create the potential difference across the membrane.

Why do intracellular anions not exit outward following potassium?

The negative charge inside the cell is provided by large organic molecules, predominantly cytoplasmic proteins. Due to their large size, they physically cannot pass through the ion channels of the membrane.

Is the membrane permeable to sodium in a state of functional rest?

No, at rest the cell membrane is impermeable to sodium ($Na^+$) ions, so all sodium remains in the extracellular fluid despite the strong concentration gradient.

What affects the exact resting potential value in different cells?

The potential value (from −50 to −100 mV) depends on the activity of the sodium-potassium ATPase and the number of potassium ion pores in a specific type of excitable tissue.

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What else to study on this topic

  • Criteria for classifying tissues into excitable and non-excitable
  • Molecular mechanism of $Na^+, K^+$-ATPase operation
  • Physics of the potassium equilibrium potential and the balance of two forces
  • Role of sodium and chloride leak currents in shifting the potential value
  • Technique of working with glass microelectrodes

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