Research articleInhibitions of PKC and CaMK-II synergistically rescue ischemia-induced astrocytic dysfunction

- Ischemia leads to the dysfunction of astrocytic glutamate transporter (Glu-T).
- Either PKC or CaMK-II inhibition partially rescues ischemic Glu-T dysfunction.
- PKC and CaMK-II inhibitions synergistically rescue ischemic Glu-T dysfunction.

Ischemic neuronal death is presumably caused by glutamate-induced excitotoxicity, in which the increased glutamate release and impaired glutamate reuptake lead to glutamate accumulation. Mechanisms underlying the ischemic deficiency of astrocytic glutamate reuptake remain unclear, which we have studied by analyzing the effect of calmodulin-dependent protein kinase II (CaMK-II) and protein kinase C (PKC) inhibitions on astrocytic glutamate transporter during ischemia. Glutamate transporter current was recorded on the astrocytes in cortical slices. KN-62 (CaMK-II inhibitor) or chelerythrine (PKC inhibitor) partially reverses the ischemic deficiency of astrocytic glutamate transporter. A combined use of PKC and CaMK-II inhibitors synergistically reverses this deficiency. Thus, one of potential therapeutic strategies is to secure the ischemia-induced deficiency of astrocytic glutamate reuptake by inhibiting PKC and CaMK-II.