The resting membrane potential is one of the most fundamental properties of a cell. This value represents the voltage difference between the inside and outside of a cell, or the intracellular and extracellular compartments.
The resting membrane potential is determined by two factors: the equilibrium potential and ion flux. The equilibrium potential refers to the voltage at which a neuron is said to be at rest, i.e., not transmitting any signals.
Ion channels in the cell membrane are responsible for ion flux, or the amount of ions that pass through the membrane per unit time. These ions contribute to either raising or lowering the resting membrane potential depending on their type.
This article will discuss how although ion channels play a role in determining the resting membrane potential, they are not a primary determinant of it. Other factors such as lipid composition and geometry of the cell membrane play larger roles in determining it.
The sodium (Na+) concentration gradient
The sodium (Na+) concentration gradient is one of the primary determinants of the resting membrane potential. The sodium (Na+) concentration is higher on the outside of the cell than on the inside of the cell.
This difference in concentrations is due to the active transport of Na+ into the cell and out of the cell. This process is carried out by the Na+/K+ ATPase pump.
The Na+/K+ ATPase pump uses energy from ATP to transport three Na+ out of the cell and two K+ into the cell. This results in a net loss of one positive charge, which causes a decrease in the concentration of Na+.
The higher concentration of Na+ outside of the cell causes there to be a pulling force on the water that surrounds it. This pulls some water out ofthe cell, decreasing its volume. Due to this reduction in volume, there is a decrease in densityofthecell.
Potassium leak channels
Potassium leak channels are a large part of what determines the resting membrane potential. Potassium leak channels are a family of proteins that allow potassium to pass through the membrane passively.
There are three main types of potassium leak channels: transient receptor potential (TRP) channels, shaker-related voltage-gated (Kv) channel family members, and the Ca2+-activated transient receptor potential (CaTRP) channel family members.
Transient receptor potential channels or TRPs are named because they have transient activation properties. This means they require some kind of stimulus to be activated and therefore allow potassium to pass through the membrane. Shaker-related voltage-gated Kv channel family members have a steady activation property, meaning they require no stimulus to be activated. The Ca2+-activated transient receptor potential channel family members are activated by calcium in the cell.
Sodium leak channels
Although it is a small component of the resting membrane potential, the sodium leak channel contributes significantly to the RMP.
These sodium leak channels are found in the cell membrane and allow for small amounts of sodium to pass through the cell membrane in either direction.
The main outward-opening sodium channel is known as a voltage-gated channel. This means that it can respond to changes in voltage across the cell membrane. It is normally closed, but when the RMP drops below -55 mV, it opens and allows Na+ to leave the cell.
Although this seems like it would lower the RMP even more, it actually prevents an even more drastic decrease in RMP due to what is called passive diffusion. This means that as Na+ leaves the cell, there is less concentration of Na+ inside of the cell, so some moves out too to achieve equilibrium.
Intracellular buffers
Another factor that contributes to the resting membrane potential is the presence of intracellular buffers. These are molecules that reside inside of the cell, as its name suggests, and act to neutralize changes in pH.
There are four primary intracellular buffers: carbon dioxide, bicarbonate, lactate, and ATP. The first three are used to neutralize increases in pH, while ATP is used to return the membrane to its normal state after a change in voltage.
Carbon dioxide and bicarbonate work together to offset increases in pH. When there is a decrease in voltage across the plasma membrane, more carbon dioxide is pumped into the intercellular space. This acts to offset the increase in pH caused by the influx of sodium ions. Bicarbonate also offsets an increase in pH by acting as a negative ion. These ions are neutralized by being combined with water molecules.
Extracellular buffers
Another factor that plays a role in the resting membrane potential is the concentration of extracellular buffers. These include sodium and potassium ions, chloride ions, and ATP.
The sodium-potassium pump (SNaK pump) actively transports three Na+ out for every one K+ entered, lowering the intracellular Na+ concentration and raising the intracellular K+ concentration.
This action results in a depletion of energy stores due to the energy required to pump these ions across the membrane. The SNaK pump also plays a role in maintaining cell volume regulation.
Cl- ions do not play a role in determining the RMP, but their presence can influence the RMP if there is an excess or deficiency of them. If there are too many Cl- ions present, then there will be more negative charge on the outside of the cell, counteracting some of the positive charge on the inside of the cell.
Non-chemical factors play a role as well
Although the chemical gradient and pumping action of the cell play a large role in determining the resting membrane potential, it is not the only factor.
Other factors that influence the resting membrane potential include temperature and activity of neighboring cells. The resting membrane potential is also influenced by temperature as increases in temperature increase the hydrogen ion concentration and decrease the sodium ion concentration, both of which increase the negative charge of the cell.
Neighboring cells can affect the RMP as well. When neighboring cells are activated, they increase their output which increases flow of ions into the cell with higher voltage gradients, decreasing its RMP.
Both of these factors play important roles in keeping the RMP stable despite changes in external conditions.
Voltage-gated ion channels
The final determinant of the resting membrane potential is voltage-gated ion channels. These are proteins in the cell membrane that regulate the flow of ions into and out of the cell.
There are several types of voltage-gated ion channels, each that allow a specific type of ion to pass through the cell membrane depending on the voltage outside of the cell.
These channels are normally closed, preventing any ions from passing through the cell membrane. When the voltage inside or outside of the cell changes, these channels open, allowing ions to pass through and alter the RMP.
These channels are opened by either a decrease in voltage inside the cell or an increase in voltage outside of the cell. This is what protects the neuron from over-excitation and death due to excessive voltages.
Voltage-gated ion channels play a role as well
Although the passive membrane potential is determined by the nature of the lipid bilayers and gap junctions, voltage-gated ion channels and other factors play a role in determining the resting membrane potential.
These include proteins in the cell membrane that regulate the flow of ions into or out of the cell. Some of these proteins are voltage-gated sodium (Na+) channels, voltage-gated calcium (Ca2+) channels, and potassium (K+) channels.
Voltage-gated sodium channels are responsible for allowing positive ions to enter the cell, thus creating a positive change in voltage. Voltage-gated calcium channels are responsible for allowing calcium ions to enter the cell, thus increasing internal pressure and creating a more negative change in voltage.
Potassium channels allow for outward flow of potassium ions, reducing internal pressure and creating a more positive change in voltage.
