What happens at resting membrane potential?

The human organism is composed of multiple cells, all of them with different components and therefore with differents resting membrane potentials. Some of these cells are excitable (e. g.: cells; neurons; muscle fibers), generating an action potential when subjected to an external stimulus, causing its membrane depolarization. The resting membrane potential (RMP) is due to changes in membrane permeability for potassium, sodium, calcium, and chloride, which results from the movement of these ions across it. Once the membrane is polarized, it acquires a voltage, which is the difference of potentials between intra and extracellular spaces.

Resting membrane potential is:

• the unequal distribution of ions on the both sides of the cell membrane;
• the voltage difference of quiescent cells;
• the membrane potential that would be maintained if there weren’t any stimuli or conducting impulses across it;
• determined by the concentrations of ions on both sides of the membrane;
• a negative value, which means that there is an excess of negative charge inside of the cell, compared to the outside.
• much depended on intracellular potassium level as the membrane permeability to potassium is about 100 times higher than that to sodium.

Producing and maintaining RMP[edit | edit source]

RMP is produced and maintained by:

Donnan effectdescribed as large impermeable negatively charged intracellular molecules attracting positively charged ions (e. g.: Na+ and K+) and repelling negative ones (e. g.: Cl−)Membrane selectivityis the difference of permeabilites between different ionsActive transport (Na+/K+ ATPase pump)is the mediated process of moving particles across a biological membrane, against the concentration gradient.

• Primary active transport – if it spends energy. This is how the Na+/K+ ATPase pump functions.
• Secondary active transport – if it involves an electrochemical gradient. This is not involved in maintaining RMP.

Ion affection of resting membrane potential[edit | edit source]

RMP is created by the distribution of ions and its diffusion across the membrane. Potassium ions are important for RMP because of its active transport, which increase more its concentration inside the cell. However, the potassium-selective ion channels are always open, producing an accumulation of negative charge inside the cell. Its outward movement is due to random molecular motion and continues until enough excess negative charge accumulates inside the cell to form a membrane potential.

Na+/K+ ATPase pump affection of the RMP[edit | edit source]

The Na+/K+ ATPase pump creates a concentration gradient by moving 3Na+ out of the cell and 2K+ into the cell. Na+ is being pumped out and K+ pumped in against their concentration gradients. Because this pump is moving ions against their concentration gradients, it requires energy.

Ion channels affection of resting membrane potential[edit | edit source]

The cell membrane contains protein channels that allow ions to diffuse passively without direct expenditure of metabolic energy. These channels allow Na + and K+ to move across the cell membrane from a higher concentration toward a lower. As these channels have selectivity for certain ions, there are potassium- and sodium- selective ion channels. All cell membranes are more permeable to K+ than to Na+ because they have more K+ channels than Na+.

Ihhs a mathematical equation applied in physiology, to calculate equilibrium potentials for certain ions.

[math]\displaystyle{ Ei = (\frac{R·T}{F·z})\cdot ln\frac{[X]1}{[X]2} }[/math]

• R = Gas Constant
• T = Absolute temperature (K)
• E = The potential difference across the membrane
• F = Faradays Constant (96,500 coulombs/mole)
• z = Valency of ion

The Goldman-Hodgkin-Katz Equation[edit | edit source]

Is a mathematical equation applied in Physiology, to determine the potential across a cell's membrane, taking in account all the ions that are permeable through it.

[math]\displaystyle{ Em = 58 log (\frac{PNa\cdot[Na]out + PK\cdot[K] out}{ PNa\cdot[Na]in + PK\cdot[K]in}) }[/math]

• E = The potential difference across the membrane
• P = Permeability of the membrane to sodium or potassium
• [ ] = Concentration of sodium or potassium inside or outside

Measuring resting potentials[edit | edit source]

In some cells, the RPM is always changing. For such, there is never any resting potential, which is only a theoretical concept. Other cells with membrane transport functions that change potential with time, have a resting potential. This can be measured by inserting an electrode into the cell. Transmembrane potentials can also be measured optically with dyes that change their optical properties according to the membrane potential.

Across the cell membrane of each neurone there exists a small difference in electrical charge, known as the membrane potential. In electrically inactive neurones, this is known as the resting membrane potential. Its typical value lies between -50 and -75 mV.

In this article, we will explore how the resting membrane potential is generated, how to calculate its approximate value and how changes in resting membrane potential may lead to significant pathology.

Overview

In overview, the resting membrane potential arises due to the differences in concentration gradient and electrochemical gradient across the cell membrane. Sodium (Na+) and chloride (Cl–) ions are present in greater concentrations extracellularly than intracellularly, whereas potassium (K+) ions are present in greater concentrations intracellularly than extracellularly.

Additionally, there are organic anions; these negatively charged molecules are most prevalent intracellularly.

The Na/K ATP-ase pump plays an essential role in maintaining the sodium and potassium concentrations by actively transporting these ions against their concentration gradients. Three sodium ions exit the cell in return for two potassium ions.

Overall, the intracellular environment is negatively charged compared to the extracellular environment, hence the resting potential of ~-50 to -75mV. If the membrane potential becomes more positive than the resting potential, the membrane is said to be depolarised, and if it becomes more negative than the resting potential the membrane is said to be hyperpolarised.

The rest of the article will explore the above concepts in more detail.

The Cell Membrane

The cell membrane acts as a selective filter, allowing the free movement of some molecules across it while tightly controlling the movement of others. Passage of a specific substance across the membrane depends on multiple factors including its electric charge, molar mass and the polarity of the molecule.

Movement of uncharged substances, like O2, CO2, urea, alcohol and glucose, depends only on their concentration gradient. The cell membrane is permeable to these molecules, and so they can move freely as their concentration gradients allow.

Charged substances such as K+, Na+, Cl– ions, cannot easily diffuse through the cell membrane due to its internal hydrophobic structure. Hence, to cross the cell membrane charged substances will utilise specialised, water-filled pores known as ion channels.

There are multiple types of ion channels depending on the type of ion that they are conducting. Importantly, ion channels are selective for a particular ion or ions.

Ion Movement

There are three factors that can induce the movement of the ions through ion channels:

• The concentration gradient – a difference in concentration of the ion on the two sides of the membrane. Ions would cross the membrane from a compartment with a higher concentration to the compartment with a lower concentration.
• The electrical gradient – an electrical potential difference across the membrane defined as the electrical potential value inside the cell relative to the extracellular environment. Positive ions will be attracted to negative electrical potential and repelled from positive electric potential, and vice versa.
• Active Transport.

Potassium

To better understand how the concentration gradient and the electrical gradient influence the movement of ions across the cellular membrane, let’s analyse the movements of potassium (K+) ions:

• The concentration gradient – The intracellular concentration of potassium greatly exceeds the extracellular concentration (~130mmol/L vs ~4mmol/L). Thus, potassium ions will tend to exit the cell according to the concentration gradient.
• The electrical gradient – As positively charged K+ ions are released, the charge of the intracellular space becomes relatively negative.  Hence, some K+ ions are attracted back towards the intracellular space, despite the concentration gradient leading them in the opposite direction.

Thus, two “streams” containing K+ ions are created; one that expels potassium as per its concentration gradient, and one which attracts potassium as per the increasing negative intracellular electrical environment.

By TeachMeSeries Ltd (2022)

Fig 1. Movements of potassium ions across the cellular membrane. Potassium ions leave the cell according to its concentration gradient. However, this is accompanied by the movement of potassium ions into the cell as they are attracted towards the increasingly-negative intracellular environment.

Equilibrium Potential

At the equilibrium potential, the rate at which ions leave by concentration gradient is equal to the rate at which ions enter via the electrochemical gradient.

Importantly, in a cell where only one type of ion can cross the membrane, the resting membrane potential will equal the equilibrium potential for that particular ion.

Nernst Equation

The Nernst equation is used to calculate the value of the equilibrium potential of a particular cell for a particular ion:

By TeachMeSeries Ltd (2022)

Equation 1: The Nernst Equation

where Vm = equilibrium potential for any ion [V]; z = valence of the ion, [C]0 = concentration of ion X outside of the cell [mol]; [C]i = concentration of ion X inside the cell [mol].

So, assuming only potassium ions could cross the membrane and knowing common values for the intracellular and extracellular concentrations of potassium, one can calculate the approximate resting potential of a cell. In the example below, K0=4 and Ki=126 are used as common values:

By TeachMeSeries Ltd (2022)

Equation 2: The Nernst equation for potassium

Resting Membrane Potential Generation

While the Nernst equation for potassium provides a good approximation, the calculation of resting membrane potential is slightly more complicated because it is not the only ion involved.

Alongside the flux of potassium ions towards the extracellular space, sodium, chloride and other ions also cross the membrane. For example, the positively charged sodium ions enter the neurones down the concentration gradient but they are also attracted by a negative electrical potential inside the neurone.

Hence, this movement will make the resting potential less negative. Overall, the resting potential accounts for the movements of all ions across the membrane.

The table below summarises the main direction of movement for various ions and the overall impact this has on the resting membrane potential of a neurone:

IonOverall direction of movementOverall impact on resting potentialPotassiumExtracellularMakes it more negativeSodiumIntracellularMakes it more positiveChlorideIntracellularMakes it more negative (small impact)Organic anionsCannot cross the membraneMakes it more negative (small impact)

Whilst all of these contribute to the resting membrane potential, the cell is most permeable to sodium and potassium ions and so these will have the greatest impact. As the cell membrane of neurones are most permeable to potassium, the resting membrane potential will be closest to the equilibrium potential for potassium ions, with the impact of sodium ion influx making it slightly less negative (i.e. -75mV as opposed to -92mV).

If there was to be any change in the permeability of the cell membrane to ions (via channels opening or closing) then the membrane potential would be altered – this is how action potentials are generated.

Maintaining the Resting Membrane Potential

Without something to maintain the ionic concentration gradients, the resting membrane potential would dissipate, and so therefore would the membrane potential. The sodium-potassium pump (Na+ K+ ATPase) prevent this and maintains the ionic differences across the membrane.

This pump actively transports potassium and sodium ions against their electrochemical gradients (i.e. potassium moves intracellularly and sodium moves extracellularly). This allows the concentration gradient that these ions travel down to be maintained and therefore, for the resting membrane potential to be maintained.

Clinical Relevance – Hyperkalaemia

Hyperkalaemia is the medical term that describes a potassium (K+) level in the blood that is higher than normal. The normal blood potassium level is normally 3.6 to 5.2 millimoles per litre (mmol/L).

In the setting of hyperkalaemia, the resting membrane potential is shifted to a less negative value as the concentration gradient driving the movement of K+ ions out of the cell is reduced. So, a normal resting potential value of −70 mV is altered to a less-negative value. This change moves the resting membrane potential closer to the threshold for action potential generation.

Thus, the neurone enters into a state of heightened excitability, so smaller deviations from this new resting potential are needed to promote action potential generation. Hence, hyperkalaemia may significantly interfere with the physiological functions of nerve cells or muscles. For example, it is known to induce dangerous arrhythmias. 

What happens during resting potential in an action potential?

What is the resting membrane potential and how is it maintained?

What does it mean when a cell is at resting potential?

What happens during resting potential quizlet?