Pathophysiological studies on Na^+-Ca^<2+> exchanger in the central nervous system

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This studies were aimed to clarify the pathophysiological roles of the Na^+-Ca^<2+> exchanger (NCX) in glial cells. The following results were obtained. 1) Receptor operated Ca^<2+> signal is regulated by NCX in the forward mode. 2) Ca^<2+> repletion after Ca^<2+> depletion causes an increase in intracellular Ca^<2+> concentration followed by cell death in cultured astrocytes. 3) This injury (Ca^<2+> paradox-like injury) is mediated by an activation of NCX in the reverse mode. 4) The Ca^<2+> paradox-like injury is attenuated by NCX inhibitors, heat shock protein and calcineurin inhibitors. 5) Heat shock protein and calcineurin inhibitors do not affect the change in intracellular Ca^<2+> induced by Ca^<2+> paradox. 6) Novel compounds inhibit NCX activity in astrocytes at nM level. 7) Hydrogen peroxide is involved in the Ca^<2+> paradox-like injury. 8) mRNA levels of rat brain NCX isoforms (NCX1, NCX2 and NCX3) are not changed by ischemia/reperfusion. 9) Competitive PCR analysis shows that main isoform of the NCX differs between neurons and astrocytes, and they have the different sensitivity to Na^+.