REVIEW ■ : The Na-Ca Exchanger in Neurons and Glial Cells

The Na⁺-Ca ²⁺ exchanger is a secondary active antiporter found in all excitable cells. This transporter couples transmembrane fluxes of Na⁺ to opposite fluxes of Ca²⁺. Under normal conditions, the energy stored in the electrochemical Na⁺ gradient is used to export Ca ²⁺ from the cytoplasm, thus contributing to cellular Ca²⁺ homeostasis, such as termination of Ca²⁺ transients during synaptic transmission in nerve terminals. The reversible and electrogenic properties of the Na⁺-Ca²⁺ exchanger suggest an interesting additional role of controlled Ca²⁺ entry, e.g., during action potential generation in axons. Moreover, under pathological conditions, such as anoxia/ischemia, the exchanger may function either to help extrude damaging Ca²⁺ loads entering via other pathways in neurons or mediate Ca²⁺ overload in axons. Cell geometry will influence the rate and extent of collapse of the Na⁺ gradient and membrane potential, the two main driving forces acting on the exchanger, which will in turn dictate to what extent and in which direction Ca²⁺ will be transported. The Na⁺-Ca²⁺ exchanger is subject to complex regulatory control by several ions and chemical messengers, and several recently identified isoforms are undoubtedly tailored for specific roles in different regions of the CNS. NEUROSCIENTIST 2:162-171, 1996