NaCa2vaihtajilla

NaCa2vaihtajilla, commonly referred to as Na+/Ca2+ exchangers (NCX), are membrane proteins that couple the movement of sodium and calcium ions across the cell membrane. They play a key role in cellular calcium homeostasis by using the inward Na+ gradient to remove Ca2+ from the cytosol, helping to regulate contraction, signaling, and excitability in many cell types. The exchanger operates bidirectionally, depending on electrochemical gradients.

The canonical mechanism involves a stoichiometry of 3 Na+ ions in for every 1 Ca2+ ion out during forward mode, which extrudes Ca2+ from the cell. In reverse mode, often driven by depolarization or high intracellular Na+, Ca2+ can be taken up into the cell in exchange for Na+ efflux. This electrogenic transport means NCX currents influence the membrane potential in addition to calcium levels.

Genetically, NCX proteins belong to the SLC8 family with three main vertebrate isoforms: NCX1 (SLC8A1), NCX2 (SLC8A2), and NCX3 (SLC8A3). NCX1 is abundant in the heart and smooth muscle, NCX2 is prominent in the brain, and NCX3 is expressed in brain and skeletal muscle, among other tissues. In addition to the plasma membrane exchangers, related mitochondrial exchangers (NCLX) help control mitochondrial calcium.

Physiologically, NCX contributes to relaxation after contraction in cardiac cells by removing cytosolic Ca2+, shapes action potential repolarization, and modulates Ca2+-dependent signaling in neurons and other cell types. Regulation occurs via intracellular Na+ and Ca2+ levels, membrane potential, and various kinases and accessory proteins. Dysregulation of NCX has been linked to cardiovascular disease and arrhythmias, making it a subject of ongoing research and pharmacological interest.