Na(+)-Ca2+ exchanger: physiology and pharmacology.

The Na(+)-Ca2+ exchanger in the plasma membrane is a bidirectional electrogenic ion transporter that couples the translocation of Na+ in one direction with that of Ca2+ in the opposite direction. This system is involved in regulation of intracellular Ca2+ concentration via the forward mode (Ca2+ extrusion) or the reverse mode (Ca2+ influx). There are two types of the plasma membrane Na(+)-Ca2+ exchanger in an animal, and they are called the cardiac type and rod outer segment type. In addition, there is an electroneutral Na(+)-Ca2+ exchanger present in mitochondria. Recent studies by the molecular biology technique show that there are at least 8 isoforms of the cardiac type (NCX1), and there are two other exchangers in the brain (NCX2 and NCX3). Due to new techniques of molecular biology and electrophysiology, much evidence is accumulating with respect to the structure, mechanism, regulation, and physiological and pathological roles of the Na(+)-Ca2+ exchanger. This review summarizes recent progress in this research field that is of pharmacological interest.