text: Loss of Calcium/Calmodulin-Dependent Protein Kinase II Activity in Cortical Astrocytes Decreases Glutamate Uptake and Induces Neurotoxic Release of ATP.
  The extent of calcium/calmodulin-dependent protein kinase II (CaMKII) inactivation in the brain following ischemia correlates with the extent of damage. We have previously shown that a loss of CaMKII activity in neurons is detrimental to neuronal viability by inducing excitotoxic glutamate release. In the current study, we extend these findings to show that the ability of astrocytes to buffer extracellular glutamate is reduced when CaMKII is inhibited. Furthermore, CaMKII inhibition in astrocytes is associated with the rapid onset of intracellular calcium oscillations. Surprisingly, this rapid calcium influx is blocked by the N-type calcium channel antagonist, omega-conotoxin. While the function of N-type calcium channels within astrocytes is controversial, these voltage-gated calcium channels have been linked to calcium-dependent vesicular gliotransmitter release. When extracellular glutamate and ATP levels are measured following CaMKII inhibition within our enriched astrocyte cultures, no alterations in glutamate levels are observed, whereas ATP levels in the extracellular environment significantly increase. Extracellular ATP accumulation associated with CaMKII inhibition contributes both to calcium oscillations within astrocytes and ultimately cortical neuron toxicity. Thus, a loss of CaMKII signaling within astrocytes dysregulates glutamate uptake and supports ATP release, two processes that would compromise neuronal survival following ischemic/excitotoxic insults.
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entities.type: CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N CHEMICAL GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
entities.text: calcium calcium N calcium N calcium calcium calcium glutamate ATP glutamate ATP Calcium Glutamate CaMKII CaMKII calcium/calmodulin-dependent protein kinase II CaMKII CaMKII CaMKII CaMKII ATP N-type calcium channel omega-conotoxin N-type calcium channels voltage-gated calcium channels CaMKII Calcium/Calmodulin-Dependent Protein Kinase II ATP calcium glutamate ATP calcium glutamate glutamate