Inhibition of rat brain inositol 1,4,5-trisphosphate 3-kinase A expression by kainic acid

Defects in intracellular calcium homeostasis may cause aberrant neuronal activation and subsequent neuronal death. Because inositol trisphosphate (IP3) regulates the release of calcium from the endoplasmic reticulum and the IP3 kinase A isoform (IP3K-A) reduces intracellular IP3, regulation of IP3K could be involved in neuronal activation and/or neuronal death. In this study, we found that kainic acid (KA) treatment in vitro and in vivo reduced the level of IP3K-A mRNA. Since KA treatment induces aberrant neuronal activation and neuronal death, we tested whether the reduction of IP3K-A mRNA was required for KA-induced neuronal death. Overexpression of adenovirus-derived IP3K-A failed to rescue neurons from KA-induced death. Because neuronal activation by KCl in vitro is sufficient to reduce IP3K-A expression, we conclude that the KA-derived reduction of IP3K-A expression is due to the aberrant neuronal activation, and the reduction in the IP3K-A mRNA level is not required for the toxic effect of KA.