Calcineurin controls inositol 1,4,5-trisphosphate type 1 receptor expression in neurons

In the central nervous system, release of Ca2+ from intracellular stores co ntributes to numerous functions? including neurotransmitter release and lon g-term potentiation and depression. We have investigated the developmental profile and the regulation of inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) in primary cultures of cerebellar granule cell s. The expression of both receptor types increases during development. Wher eas the expression of type 1 IP3R appears to be regulated by Ca2+ influx th rough I, type channels or N-methyl-D-aspartate (NMDA) receptors, RyR levels increase independently of Ca2+, The main target of Ca2+-influx-regulating IP3R expression is the Ca2+ calmodulin-dependent protein phosphatase calcin eurin, because pharmacological blockade of this protein abolishes IP3R expr ession. Although calcineurin has been shown to regulate the phosphorylation state of the IP3R, the effect described here is at the transcriptional lev el because IP3R mRNA changes in parallel with protein levels. Thus, calcine urin plays a dual role in IP3R-mediated Ca2+ signaling: it regulates IP3R f unction by dephosphorylation in the short-term time scale and IP3R expressi on over more extended periods.