NCX2

NCX2 is a member of the sodium/calcium exchanger family that mediates bidirectional transport of Na+ and Ca2+ across the plasma membrane, typically extruding Ca2+ in exchange for Na+ when the electrochemical gradients favor it. In certain conditions, such as high intracellular Na+ or depolarization, NCX2 can operate in reverse to bring Ca2+ into the cell.

In humans, NCX2 is encoded by the SLC8B1 gene. It exists as multiple splice variants with tissue-specific expression patterns. Expression is strongest in the brain, particularly in regions such as cortex and hippocampus; lower levels are found in heart and skeletal muscle.

The protein helps regulate resting and activity-related intracellular Ca2+ in neurons, contributing to control of neuronal excitability, synaptic transmission, and plasticity. Although NCX1 is the primary calcium exchanger in the heart, NCX2 also contributes to Ca2+ homeostasis in cardiac tissue under certain conditions.

Regulation of NCX2 involves intracellular Na+ and Ca2+ concentrations, membrane potential, and post-translational modulation; alternative splicing generates isoforms with distinct regulatory properties that may tailor Ca2+ handling to tissue needs.

Clinically, altered NCX2 expression or function has been investigated in models of cerebral ischemia, epilepsy, and neurodegenerative diseases, where impaired calcium extrusion can exacerbate Ca2+-mediated injury. The precise role of NCX2 in human disease remains under investigation.

See also: Sodium-calcium exchanger; SLC8B1; NCX1; NCX3.