Calcineurin controls the transcription of Na+/Ca2+ exchanger isoforms in developing cerebellar neurons

The Na+/Ca2+ exchanger (NCX) and the plasma membrane Ca2+-ATPase export Ca2 + from the cytosol to the extracellular space. Three NCX genes (NCX1, NCX2, and NCX3), encoding proteins with very similar properties, are expressed a t different levels in tissues. Essentially, no information is available on the mechanisms that regulate their expression. Specific antibodies have bee n prepared and used to explore the expression of NCX1 and NCX2 in rat cereb ellum. The expression of NCX2 became strongly up-regulated during developme nt, whereas comparatively minor effects were seen for NCX1. This was also o bserved in cultured granule cells induced to mature in physiological concen trations of potassium. By contrast, higher K+ concentrations, which induce partial depolarization of the plasma membrane and promote the influx of Ca2 +, caused the complete disappearance of NCX2, Reverse transcription-polymer ase chain reaction analysis showed that the process occurred at the transcr iptional level and depended on the activation of the Ca2+ calmodulin-depend ent protein phosphatase, calcineurin. The NCX1 and NCX3 genes were also aff ected by the depolarizing treatment: the transcription of the latter became upregulated, and the pattern of expression of the splice variants of the f ormer changed. The effects on the NCX1 and NCX3 genes were calcineurin-inde pendent.