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

Secondary active transport

Secondary active transport

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

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.

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).

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

GABA

GABA is an inhibitory amino acid neurotransmitter in the central and peripheral nervous systems. It is the most abundant inhibitory neurotransmitter in the nervous system. During embryonic development, GABA acts as an excitatory neurotransmitter at some central synapses. GABA is a classical neurotransmitter. Its action is exerted via the activation of GABA_A, GABA_B, and GABA_C receptors. GABA_A and GABA_C receptors are ligand-gated chloride channels, whereas GABA_B receptors are G protein coupled receptors. At GABAergic synapses, the action of GABA is terminated by GABA transporters (GAT), which transport GABA from the extracellular space in synaptic and extrasynaptic regions into neurons and glia.

Glutamate (Glu, E) is one of the standard twenty (20) amino acids used by cells to synthesize peptides, polypeptides, and proteins. It has a molecular weight of 147.13 g/mol. Its side chain has a pK_a of 4.07 and, therefore, glutamate has a net negative charge at physiological pH.

In the nervous system, glutamate is an excitatory amino acid neurotransmitter. In fact, glutamate is the most abundant excitatory neurotransmitter in the nervous system. Glutamate is a classical neurotransmitter. Its action is exerted via the activation of glutamate receptors (GluR), some of which are ligand-gated ion channels (ionotropic receptors), and some are G protein coupled receptors (GPCRs, metabotropic receptors). At glutamatergic synapses, the action of glutamate is terminated by glutamate transporters (EAAT, excitatory amino acid transporter), which transport glutamate from the extracellular space in synaptic and extrasynaptic regions into neurons and glia.

Glycine (Gly, G) is one of the standard twenty (20) amino acids. At a molecular weight of 75.07 g/mol, it is the smallest of the 20 amino acids used by cells to synthesize peptides, polypeptides, and proteins.

In the nervous system, glycine is also an inhibitory amino acid neurotransmitter. Glycinergic synapses are most commonly found in brain stem and spinal cord circuits. Glycine is a classical neurotransmitter. Its action is exerted via the activation of ionotropic glycine receptors (GlyR), which are ligand-gated chloride channels. At glycinergic synapses, the action of glycine is terminated by glycine transporters (GlyT), which transport glycine from the extracellular space in synaptic and extrasynaptic regions into neurons and glia.

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.

Ouabain binds to and inhibits the transport activity of the Na⁺/K⁺/ATPase (i.e., sodium pump).

Ouabain is plant derived and belongs to the class of drugs referred to as cardiac glycosides. Similar to other cardiac glycosides, ouabain increase heart muscle contractility. However, ouabain is used only experimentally and not in humans (as for example digoxin is for the treatment of congestive heart failure).

There is some evidence that ouabain may be produced endogenously in humans.

Vanadate

Ouabain (Wikipedia)

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.

Cotransport

Cotransport