Antiporters

Antiporters, also known as exchangers, are membrane transport proteins that move two or more substrates in opposite directions across a cell membrane. They function as part of secondary active transport, coupling the movement of one substrate down its electrochemical gradient to drive the transport of another substrate against its gradient. In contrast to symporters, which move both substrates in the same direction, antiporters enact counter-transport.

Most antiporters operate by an alternating-access mechanism: substrate binding on one side stabilizes a specific conformation, which then opens to the opposite side and releases the substrates in reverse order. The energy source is typically the gradient of the driving ion (often Na+ or H+), though some exchangers can run near equilibrium in certain conditions. Stoichiometry can vary; common configurations include one molecule exchanged for one molecule, or more complex ratios such as 3 Na+ per Ca2+.

Examples include the Na+/H+ exchanger (NHE), which extrudes H+ in exchange for Na+ uptake and helps regulate intracellular pH; the Na+/Ca2+ exchanger (NCX) that uses the Na+ gradient to expel Ca2+ from cardiac cells; and the Cl-/HCO3- exchangers (anion exchangers) that contribute to acid-base balance in erythrocytes and other tissues. Bacteria possess Nha-type Na+/H+ antiporters that help with pH and Na+ homeostasis.

Physiological roles of antiporters include pH regulation, cell volume maintenance, and ion homeostasis. Defects in antiporter function are associated with various diseases, and these transporters are targets of some pharmacological interventions. Research continues to elucidate their structures, regulation, and roles in physiology.