Physiology, Resting Potential

Article Author:
Steven Chrysafides
Article Editor:
Sandeep Sharma
2/12/2019 7:45:28 AM
PubMed Link:
Physiology, Resting Potential


Neurons and muscle cells are excitable cells such that these cell types can transition from a resting state to an excited state. The resting membrane potential of a cell is defined as the electrical potential difference across the plasma membrane when that cell is in a non-excited state. Traditionally, the electrical potential difference across a cell membrane is expressed by its value inside the cell relative to the extracellular environment. Resting membrane potentials typically fall within the range of -70 to -80 mV, meaning that the intracellular environment of the cell at rest is 70 to 80 mV lower than the extracellular environment.[1][2]


There are a handful of crucial ions which contribute to the resting potential, with sodium (Na+) and potassium (K+) being especially noteworthy. Also significant are the various negatively charged intracellular proteins and organic phosphates that cannot cross the cell membrane. To understand how the resting membrane potential gets generated and why its value is negative, it is crucial to have an understanding of equilibrium potentials, permeability, and ion pumps.[1]

Organ Systems Involved

All cells within the body have a characteristic resting membrane potential depending on their cell type. Of primary importance, however, are neurons and all three types of muscle cells: smooth, skeletal, and cardiac. Hence, resting membrane potentials are crucial to the proper functioning of the nervous and muscular systems.


The significance of the resting membrane potential is that it allows the body’s excitable cells (neurons and muscle) to experience rapid changes to perform their proper role. Upon excitation, these cells deviate from their resting membrane potential to undergo a rapid, temporary action potential before coming back to rest. In effect, this is similar to an on-off switch.

For neurons, the firing of an action potential allows that cell to communicate with other cells via the release of various neurotransmitters. In muscle cells, the generation of an action potential causes the muscle to contract.


For the vast majority of solutes, intracellular and extracellular concentrations are different. Because of this, there is often a driving force for the movement of solutes across the plasma membrane. The direction of this driving force involves two components: the concentration gradient and the electrical gradient. Regarding the concentration gradient, a solute will move from an area where it is more concentrated to a separate area with a lower concentration. Regarding the electrical gradient, a charged solute will move from an area with a similar charge towards a separate area with an opposite charge. All solutes are affected by concentration gradients, but only charged solutes are affected by electrical gradients.

ABsent any other forces, a solute that can cross the plasma membrane will do so until it reaches equilibrium. For a non-charged solute, equilibrium will take place when the concentration of that solute becomes equal on both sides of the membrane; this is because the concentration gradient is the only factor that produces a driving force for the movement of non-charged solutes. However, for charged solutes, both the concentration and electrical gradients must be taken into account, as both influence the driving force. A charged solute is said to have achieved electrochemical equilibrium across the membrane when its concentration gradient is exactly equal and opposite that of its electrical gradient. It’s important to note that when this occurs, it does not mean that the concentrations for that solute will be the same on both sides of the membrane. During electrochemical equilibrium for a charged solute, there is usually still a concentration gradient, but an electrical gradient oriented in the opposite direction negates it. Under these conditions, the electrical gradient for a given charged solute serves as an electrical potential difference across the membrane. The value of this potential difference represents the equilibrium potential for that charged solute.

Under physiological conditions, the ions contributing to the resting membrane potential rarely reach electrochemical equilibrium. One reason for this is that most ions cannot freely cross the cell membrane because it is not permeable to most ions. For instance, Na+ is a positively charged ion that has an intracellular concentration of 14 mM, an extracellular concentration of 140 mM, and an equilibrium potential value of +65 mV. This difference means that when the inside of the cell is 65 mV higher than the extracellular environment, Na+ will be in electrochemical equilibrium across the plasma membrane. Moreover, K+ is a positively charged ion that has an intracellular concentration of 120 mM, an extracellular concentration of 4 mM, and an equilibrium potential of -90 mV; this means that K+ will be in electrochemical equilibrium when the cell is 90 mV lower than the extracellular environment. 

In the resting state, the plasma membrane has slight permeability to both Na+ and K+. However, the permeability for K+ is much greater, which occurs because of the presence of K+ “leak” channels embedded in the plasma membrane, which allow K+ to diffuse out of the cell down its electrochemical gradient. Because of this enhanced permeability, K+ is close to electrochemical equilibrium, and the membrane potential is close to the K+ equilibrium potential of -90 mV. The cell membrane at rest has a very low permeability for Na+, which means Na+ is far from electrochemical equilibrium and the membrane potential is far from the Na+ equilibrium potential of +65 mV.[2]

The equilibrium potentials for Na+ and K+ represent two extremes, with the cell’s resting membrane potential falling somewhere in between. Since the plasma membrane at rest has a much greater permeability for K+, the resting membrane potential (-70 to -80 mV) is much closer to the equilibrium potential of K+ (-90 mV) than it is for Na+ (+65 mV). This factor brings up an important point: the more permeable the plasma membrane is to a given ion, the more that ion will contribute to the membrane potential (the overall membrane potential will lean closer to the equilibrium potential of that ion).

Na+ and K+ do not reach electrochemical equilibrium. Even though a small amount of Na+ can enter the cell and a current of K+ can leave the cell via K+ leak channels, the Na+/K+ pump constantly uses energy to maintain these gradients. By using a molecule of ATP, this pump can extrude three Na+ ions from the cell and, in exchange, bring two K+ ions into the cell. In this way, the Na+/K+ pump functions to maintain the resting membrane potential.[3]

Clinical Significance

Both the generation and maintenance of the resting membrane potential are especially important in excitable cells (neurons and muscle). Conditions that alter the resting membrane potential of these cells can have a profound impact on their proper functioning. For instance, hypokalemia is a state in which there is a lower than normal amount of K+ in the blood. As a result, there is an enhanced concentration gradient that favors the flux of K+ out of cells. This results in hyperpolarization of the cells, greater stimulus required to achieve action potential. This leads to a more negative potential in cardiac muscles from a more complete recovery of sodium channel inactivation. The low potassium level leads to delayed ventricular repolarization and can lead to reentrant arrhythmias.[4]

Increased levels of potassium results in depolarization of the membrane of cells. This depolarization inactivates sodium channels, which makes cells refractory leading to major arrhythmias.[5]

Major electrolytes abnormalities can lead to muscle spasms of skeletal muscles, dysrhythmias of cardiac muscles and seizure of CNS neurons.


[1] Wright SH, Generation of resting membrane potential. Advances in physiology education. 2004 Dec;     [PubMed PMID: 15545342]
[2] Enyedi P,Czirják G, Molecular background of leak K currents: two-pore domain potassium channels. Physiological reviews. 2010 Apr;     [PubMed PMID: 20393194]
[3] Morth JP,Pedersen BP,Toustrup-Jensen MS,Sørensen TL,Petersen J,Andersen JP,Vilsen B,Nissen P, Crystal structure of the sodium-potassium pump. Nature. 2007 Dec 13;     [PubMed PMID: 18075585]
[4] Castro D,Sharma S, Hypokalemia . 2018 Jan     [PubMed PMID: 29494072]
[5] Simon LV,Farrell MW, Hyperkalemia . 2018 Jan     [PubMed PMID: 29261936]