Calcium controls the transcription of its own transporters and channels in developing neurons

Calcium has now become important as a regulator of gene expression. Cerebellar granule cells developing in culture undergo early apoptosis unless their calcium is permitted to increase, e.g., by depolarizing their plasma membrane. The increase is kept within controlled limits by changing the pattern of transcription of calcium transporters: The IP₃ channel (but not the ryanodine channel) becomes strongly up-regulated after some days in culture in a reaction which is controlled by calcineurin. Two plasma membrane calcium pumps (isoforms PMCA2 and PMCA3) also become strongly up-regulated after some days; one (PMCA1) experiences instead a splicing switch which up-regulates a truncated variant of the isoform. By contrast, one splicing variant of the isoform PMCA4 and one of the Na/Ca exchangers of the plasma membrane (NCX2) become very rapidly down-regulated: Their down-regulation is also controlled by calcineurin. The altered pattern of Ca²⁺ transporter expression is likely to reflect development-linked changes in the demands for calcium signaling in different domains of the neuronal cell.