The voltage difference across a cell plasma membrane.

The membrane potential is generally inside negative with respect to the outside, where the outside potential is generally set as the reference value. In electrically excitable cells, the value of the membrane potential can be positive (inside with respect to the outside) during electrical activity (i.e., during action potentials).

Resting membrane potential

Resting membrane potential

The voltage difference across a cell plasma membrane in the resting or quiescent state. It is also simply referred to as the resting potential (V_rest). The value of the resting membrane potential varies from cell to cell. Depending on the cell type, it can range from −90 mV to −20 mV.

For example, V_rest is −90 mV in skeletal and cardiac muscle cells as well as in astrocytes. In a typical neuron, V_rest is approximately −70 mV. In many non-excitable cells, V_rest ranges from −60 to −50 mV. In photoreceptors, V_rest is about −20 mV.

Resting membrane potential

The action potential is a rapid and reversible reversal of the electrical potential difference across the plasma membrane of excitable cells such as neurons, muscle cells and some endocrine cells. In a neuronal action potential, the membrane potential rapidly changes from its resting level of approximately -70 mV to around +50 mV and, subsequently, rapidly returns to the resting level again. The neuronal action potential forms an important basis for information processing, propagation, and transmission. In muscle cells, the action potential precedes, and is necessary to bring about, muscle contraction. Some endocrine cells also exhibit action potentials, where the excitation leads to hormone secretion.

The action potential is also referred to as the electrical impulse or nervous impulse.

Graded potential

Neuronal Action Potential

An integral membrane protein which contains a pore through which ions, water, or polar molecules permeate. For any given channel, the pore is usually very selective for the particular ion or molecule. For example, sodium (Na⁺) channels are very selective for Na⁺ over other cations.

The channel pore may be constitutively open, or it may be gated to the open state by various stimuli such as chemical ligands, voltage, temperature, or mechanical stimulation of the membrane.

Refers to the concentration gradient of an ion or molecule. The concentration gradient may exist across a biological membrane, where the concentration is higher on one side of the membrane compared to the other side. Concentration gradient may also exist in a solution without an apparent barrier separating the area of higher concentration from the area of lower concentration. In both cases, the free energy that results from the concentration difference drives the movement of the ion/molcule from the area of higher concentration to the area of lower concentration. In free solution, the ion/molecule simply diffuses down its gradient. Movement across a biological membrane is more complicated and is a function of lipid solubility of the ion/molecule as well as the presence of channels or transport proteins that can allow the ion/molecule to cross the membrane (see Lipid Bilayer Permeability and Summary of Membrane Transport Processes).

Electrical gradient
Electrochemical gradient

CI⁻

The main anion (negatively charged ion) of the extracellular fluid.

Cloride (Cl⁻) plays an important role in several physiological processes such as the action potential of skeletal muscle cells, CO₂ transport in blood (via Cl⁻/bicarbonate exchange across the plasma membrane of red blood cells), and many other processes.

The extracellular concentration of Cl⁻ is about 110 mM. The intracellular concentration of Cl⁻ is about 10 mM.

Refers to neurons, synapses, or receptors where acetylcholine is used as the neurotransmitter.

For example, cholinergic neurons release acetylcholine as their neurotransmitter.

In cholinergic synapses, acetylcholine is released from the presynaptic neuron, and it acts on acetylcholine receptors in the plasma membrane of the postsynaptic cell.

Cholinergic receptors are those that respond to acetylcholine as the physiological ligand. The two major types are nicotinic and muscarinic cholinergic receptors (may also be referred to as nicotinic and muscarinic acetylcholine receptors).

Cholinergic drugs are compounds that mimic the action of acetylcholine by binding to and activating cholinergic receptors.

A type of secondary active transport across a biological membrane in which a transport protein couples the movement of an ion (usually Na⁺ or H⁺) down its electrochemical gradient to the movement of another ion or molecule against a concentration or electrochemical gradient. The ion moving down its electrochemical gradient is referred to as the driving ion. The ion/molecule being transported against a chemical or electrochemical gradient is referred to as the driven ion/molecule.

In cotransport, the direction of transport is the same for both the driving ion and driven ion/molecule (into the cell or out of the cell).

An example is the Na⁺/glucose cotransporter (SGLT), which couples the movement of Na⁺ into the cell down its electrochemical gradient to the movement of glucose into the cell against its concentration gradient.

Cotransport is also commonly referred to as symport.

Transport proteins that are involved in this type of transport are referred to as cotransporters or symporters.

Symport

Secondary active transport
Exchange

Lecture notes on Secondary Active Transport

An electrophysiological technique in which the current passing across the cell membrane is controlled experimentally, and the membrane voltage is measured.

Voltage clamp

Neuronal Action Potential - Pharmacological Inhibition of Na⁺ and K⁺ Channels

Refers to a change in the value of the membrane potential, where the membrane potential becomes less negative (or more positive) than the resting membrane potential.

Repolarization
Hyperpolarization

Resting Membrane Potential - Introduction
Figure showing depolarization, repolarization, and hyperpolarization

Movement of a substance out of the cell.

Efflux is reported as a rate. It is the amount of substance that moves through a given area of the plasma membrane per unit time.

Flux
Influx
Unidirectional flux
Net flux

In biological solutions, electrical gradient refers to the electrical potential that acts on an ion to drive the movement of the ion in one or another direction (see Resting Membrane Potential - Establishment of the Membrane Potential).

Chemical gradient
Electrochemical gradient

V_DF

When an ion is not at its electrochemical equilibrium, an electrochemical driving force (V_DF) acts on the ion, causing the net movement of the ion across the membrane down its own electrochemical gradient.

The electrochemical driving force is generally expressed in millivolts and is calculated according the following equation:

V_DF = V_m − V_eq

where V_DF is the electrochemical driving force, V_m is the membrane potential, and V_eq is the equilibrium potential.

Membrane potential
Equilibrium potential
Electrochemical gradient

Resting Membrane Potential - Electrochemical Driving Force Acting on Ions
Electrochemical Driving Force Calculator

Refers to the balance of chemical and electrical gradients that act on an ion, particularly as it relates to the movement of an ion across a biological membrane (see Resting Membrane Potential - Establishment of the Membrane Potential and Resting Membrane Potential - Nernst Equilibrium Potential).

Chemical gradient
Electrical gradient

Electrogenic pumps are primary active transporters that hydrolyze ATP and use the energy released from ATP hydrolysis to transport ions across biological membranes leading to the translocation of net charge across the membrane.

For example, the Na⁺/K⁺ ATPase (sodium pump) is an electrogenic pump because during every transport cycle, it transports 3 Na⁺ ions out of the cell and 2 K⁺ ions into the cell. This leads to the movement of one net positive charge out of the cell making this process electrogenic.

Electrogenic

An electrogenic transport process is one that leads to the translocation of net charge across the membrane. For example, ion channels such as Na⁺, K⁺, Ca²⁺, and Cl⁻ channels are electrogenic.

The Na⁺/K⁺ ATPase is electrogenic because for every ATP molecule hydrolyzed, 3 Na⁺ ions are transported out of the cell and 2 K⁺ ions are transported into the cell (leading to the translocation of one net positive charge out of the cell).

Many secondary active transporters are also electrogenic. For example, the Na⁺/glucose cotransporter (found in the small intestine and kidney proximal tubules), transports 2 Na⁺ ions and 1 glucose molecule into the cell across the plasma membrane (leading to the translocation of two net positive charges into the cell per transport cycle).

Electrophysiology is the study of the electrical properties of biological macromolecules, cells, tissues, and organs. Electrical signals such as voltage and/or current are generally measured. Examples include measuring changes in the membrane voltage of excitable cells (e.g., neurons, muscle cells, and some endocrine cells) during an action potential. The current carrried by ions as they permeate the pore of ion channels can also be measured - both at the single-channel level (single-channel current), as well as the macroscopic current resulting from the activity of a population of channels. As another example, electrical measurements may involve recording voltage changes at the surface of the skin that result from the activity of skeletal muscles (electromyogram, EMG), cardiac myocytes (electrocardiogram, ECG), or neurons in the brain (electroencephalogram, EEG).

V_eq. or E_eq.

Refers to the membrane potential at which there is no net movement of an ion across the plasma membrane into or out of the cell.

Resting Membrane Potential - Establishment of the Membrane Potential
Resting Membrane Potential - Nernst Equilibrium Potential
Nernst Potential Calculator

A type of secondary active transport across a biological membrane in which a transport protein couples the movement of an ion (usually Na⁺ or H⁺) down its electrochemical gradient to the movement of another ion or molecule against a concentration or electrochemical gradient. The ion moving down its electrochemical gradient is referred to as the driving ion. The ion/molecule being transported against a chemical or electrochemical gradient is referred to as the driven ion/molecule.

In exchange, the driving ion and the driven ion/molecule are transported across the biological membrane in opposite directions.

An example is the Na⁺/Ca²⁺ exchanger (NCX), which couples the movement of 3 Na⁺ ions into the cell down its electrochemical gradient to the movement of 1 Ca²⁺ ion out of the cell against its electrochemical gradient.

Exchange is also commonly referred to as antiport.

Transport proteins that are involved in this type of transport are referred to as exchangers or antiporters.

Antiport

Secondary active transport
Cotransport

Lecture notes on Secondary Active Transport

Facilitated diffusion (or facilitated transport) is a form of passive transport across biological membranes and refers to carrier-mediated transport of molecules/ions down a concentration gradient. Facilitated transport is mediated by facilitative transporters (also referred to as uniporters).

Facilitated Diffusion

The rate of movement of a substance across an interface. The interface could be the plasma membrane (separating the intracellular or extracellular fluid compartments), an epithelial sheet separating two compartments, or where two solutions of different composition meet.

Flux is reported as a rate. It is the amount of substance that moves across a given interface per unit time.

Influx
Efflux
Unidirectional flux
Net flux

The Hodgkin cycle represents a positive feedback loop in neurons, where an initial membrane depolarization from the resting value (∼ −70 mV) to the threshold value (∼ −50 mV) leads to rapid depolarization of the membrane potential to approach the equilibrium potential for Na⁺ (V_Na ≈ +60 mV). The voltage-gated Na⁺ channels of neurons are responsible for the Hodgkin cycle.

See the figure depicting the Hodgkin cycle.

Important Features of the Neuronal Action Potential

Refers to a change in the value of the membrane potential, where the membrane potential becomes more negative than the resting membrane potential.

Depolarization
Repolarization

Resting Membrane Potential - Introduction
Figure showing depolarization, repolarization, and hyperpolarization

Not permeable. Not allowing the passage of substances. Impermeable refers to a property of a membrane or channel pore in preventing or restricting the passage of substances. For example, the lipid bilayer portion of biological membranes is highly impermeable to ions and large polar molecules.

See also permeable.

Permeable
Permeability
Permeant
Impermeant

Lipid Bilayer Permeability

Not permeant. Incapable of passing through or penetrating. Impermeant refers to the inability of a substance (e.g., ion or molecule) to cross (i.e., permeate or penetrate) a biological membrane or channel pore. For example, it can be said that ions are membrane impermeant.

See also permeant.

Permeant
Permeability
Permeable
Impermeable

Lipid Bilayer Permeability

Movement of a substance into the cell.

Influx is reported as a rate. It is the amount of substance that moves through a given area of the plasma membrane per unit time.

Flux
Efflux
Unidirectional flux
Net flux

Refers to the ability of the thyroid gland to accumulate iodide (I⁻) against a steep electrochemical gradient. While the iodide concentration in plasma and interstitial fluid is approximately 300 nL, iodide concentration in the cytoplasm of thyroid follicular cells, as well as the lumen of thyroid follicles can be many folds higher. The protein that enables iodide transport into the thyroid gland against an electrochemical gradient is the Na⁺/iodide symporter (NIS), which is located in the basolateral membrane of thyroid follicular cells. Within the lumen of thyroid follicles, iodide is incorporated into the tyrosine residues of thyroglobulin during thyroid hormone biosynthesis, hence, allowing very high iodide concentrations in the colloid.

Plasma membrane of a muscle cell. It is also referred to as sarcolemma.

Sarcolemma

An equation used to calculate the equilibrium potential (V_eq.) of an ion. The equilibrium potential for an ion is also referred to as the Nernst potential for that ion. It is the membrane potential at which no net movement of the ion in question occurs across the membrane.



where V_eq. is the equilibrium potential, R is the universal gas constant, T is the temperature in Kelvin, z is the valence of the ionic species, F is the Faraday's constant, and [X]_o and [X]_i are the extracellular and intracellular, respectively, concentrations of the ion in question.

Resting Membrane Potential - Nernst Equilibrium Potential
Derivation of the Nernst Equation

Net flux represents the amount of substance moved in or out of the cell. It is the mathematical difference between influx and efflux.

Net flux = Influx − Efflux

Similar to influx and efflux, net flux is reported as a rate. It is the net amount of substance that moves through a given area of the plasma membrane per unit time.

Flux
Influx
Efflux
Unidirectional flux

Refers to that part of the action potential where the membrane potential is positive (inside with respect to the outside).

See figure.

Neuronal Action Potential - Important Features of the Neuronal Action Potential

Permeability refers to the ease with which molecules cross biological membranes. It may also refer to the ease with which ions or molecules pass through the pore of channel proteins.

Permeable
Impermeable
Permeant
Impermeant

Lipid Bilayer Permeability

Permeable refers to a property of a membrane or channel pore in allowing substances to pass through. For example, the lipid bilayer portion of biological membranes is highly permeable to fat-soluble molecules, but is not permeable to ions and large polar molecules.

See also impermeable.

Impermeable
Permeability
Permeant
Impermeant

Lipid Bilayer Permeability

Permeant refers to the ability of a substance (e.g., ion or molecule) to cross (i.e., permeate or penetrate) a biological membrane or channel pore. For example, it can be said that fat-soluble molecules are membrane permeant.

See also impermeant.

Impermeant
Permeability
Permeable
Impermeable

Lipid Bilayer Permeability

Refers to the return of the membrane potential toward the normal resting value after a membrane depolarization.

Depolarization
Hyperpolarization

Resting Membrane Potential - Introduction
Figure showing depolarization, repolarization, and hyperpolarization

Plasma membrane of a muscle cell. It is also referred to as myolemma.

Myolemma

Secondary active transport is a type of active transport across a biological membrane in which a transport protein couples the movement of an ion (typically Na⁺ or H⁺) down its electrochemical gradient to the movement of another ion or molecule against a concentration or electrochemical gradient. The ion moving down its electrochemical gradient is referred to as the driving ion. The ion/molecule being transported against a chemical or electrochemical gradient is referred to as the driven ion/molecule.

This transport process is referred to as active transport because the driven ion/molecule is transported against a concentration or electrochemical gradient. It is referred to as secondary active transport because no ATP hydrolysis is involved in this process (as opposed to primary active transport). The energy required to drive transport resides in the transmembrane electrochemical gradient of the driving ion.

Secondary active transport is also referred to as ion-coupled transport. Those utilizing Na⁺ as the driving ion are called Na⁺-coupled transporters. Those utilizing H⁺ as the driving ion are called H⁺-coupled transporters.

Two types of secondary active transport exist: cotransport (also known as symport) and exchange (also known as antiport). Na⁺/glucose cotransporter and H⁺/dipeptide cotransporter are examples of cotransporters. Na⁺/Ca²⁺ exchanger and Na⁺/H⁺ exchanger are examples of exchangers.

Cotransport
Symport
Exchange
Antiport

Lecture notes on Secondary Active Transport

Secretion refers to cellular release of substances (ions and small and large molecules) to the external environment of the cell. Secretion may be accomplished by exocytosis (fusion of transport vesicles with the plasma membrane and release of vesicle contents to the external environment), by transport of molecules across the plasma membrane (via the activity of transport proteins such as pumps, transporters, and channels), or by simple diffusion of fat-soluble molecules through the plasma membrane out of the cell.

For example, endocrine cells secrete hormone molecules that then enter the bloodstream. Neurons release (i.e., secrete) neurotransmitter molecules into the synaptic cleft. Some neurons secrete neurohormones; which similar to hormones, travel in the bloodstream to reach distant target cells. Epithelial cells secrete molecules in luminal spaces, such as digestive enzymes secreted into the digestive tract by various cell types.

Excretion

Na⁺

The main cation (positively charged ion) of the extracellular fluid.

Sodium (Na⁺) plays an important role in several physiological processes such as the action potential of neurons and muscle cells, secondary active, sodium-coupled transport of ions, nutrients, neurotransmitters across the plasma membrane of cells, and many other processes.

The extracellular concentration of Na⁺ is about 145 mM. The intracellular concentration of Na⁺ is about 15 mM.

Refers to the rapid depolarization of the membrane early in the action potential. In neuronal, skeletal muscle, and cardiac muscle action potentials, the Hodgkin cycle is responsible for the spike phase of the action potential.

See figure.

Important Features of the Neuronal Action Potential

Sub-threshold (or subthreshold) refers to a stimulus that is too small in magnitude to produce an action potential in excitable cells.

In general, a sub-threshold stimulus leads to the depolarization of the membrane, but the magnitude of the depolarization is not large enough to reach the threshold voltage. Therefore, sub-threshold stimuli do not elicit action potentials.

Threshold
Supra-threshold

Neuronal Action Potential - Introduction

Supra-threshold (or suprathreshold) refers to a stimulus that is large enough in magnitude to produce an action potential in excitable cells.

In general, a supra-threshold stimulus leads to the depolarization of the membrane, and the magnitude of the depolarization is larger than that necessary to simply reach the threshold voltage. Therefore, supra-threshold stimuli elicit action potentials.

Threshold
Sub-threshold

Neuronal Action Potential - Introduction

Tastants are taste-provoking chemical molecules that are dissolved in ingested liquids or saliva.

Tastants stimulate the sense of taste. It can also be said that tastants elicit gustatory excitation.

A tastant is the appropriate ligand for receptor proteins located on the plasma membrane of taste receptor cells.

The membrane voltage that must be reached in an excitable cell (e.g., neuron or muscle cell) during a depolarization in order to generate an action potential. At the threshold voltage, voltage-gated channels become activated. Threshold is approximately −50 to −40 mV in most excitable cells.

Sub-threshold
Supra-threshold

Neuronal Action Potential - Introduction

The rate of movement of a substance across an interface in only one, and not the opposite, direction (i.e., flux in only one direction). For example, when referring to the plasma membrane of cells, we can think of unidirectional flux of a substance ino the cell (referred to as influx), as well as unidirectional flux of the substance out of the cell (referred to as efflux). The difference between two unidirectional fluxes is referred to as net flux, which is the net amount that moves into or out of the cell.

Flux
Influx
Efflux
Net flux

An electrophysiological technique in which the voltage of a cell membrane is controlled experimentally, and the current passing across the membrane is measured.

Current clamp

Neuronal Action Potential - Pharmacological Inhibition of Na⁺ and K⁺ Channels