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 IP ₃K-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.