Ca(2+) influx through AMPA or kainate receptors alone is sufficient to initiate excitotoxicity in cultured oligodendrocytes.Neurobiol Dis. 2002 Mar; 9(2):234-43.ND
Oligodendrocytes are vulnerable to excitotoxic insults mediated by AMPA receptors and by low and high affinity kainate receptors, a feature that is dependent on Ca(2+) influx. In the current study, we have analyzed the intracellular concentration of calcium [Ca(2+)](i) as well as the entry routes of this cation, upon activation of these receptors. Selective activation of either receptor type resulted in a substantial increase (up to fivefold) of [Ca(2+)](i), an effect which was totally abolished by the non-NMDA receptor antagonist CNQX or by removing Ca(2+) from the culture medium. Blockade of voltage-gated Ca(2+) channels with La(3+) or nifedipine, reduced the amplitude of the Ca(2+) current triggered by AMPA receptor activation by approximately 65%, but not that initiated by low and high affinity kainate receptors. In contrast, KB-R7943, an inhibitor of the plasma membrane Na(+)-Ca(2+) exchanger, solely attenuated the rise in [Ca(2+)](i) by approximately 25% due to activation of low affinity kainate receptors. However, oligodendroglial death by glutamate receptor overactivation was largely unaffected in the presence of La(3+) or KB-R7943. These findings indicate that Ca(2+) influx via AMPA and kainate receptors alone is sufficient to initiate cell death in oligodendrocytes, which does not require the entry of calcium via other routes such as voltage-activated calcium channels or the plasma membrane Na(+)-Ca(2+) exchanger.