Ca(2+) influx through AMPA or kainate receptors alone is sufficient to initiate excitotoxicity in cultured oligodendrocytes.
Neurobiol Dis
; 9(2): 234-43, 2002 Mar.
Article
en En
| MEDLINE
| ID: mdl-11895374
ABSTRACT
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.
Buscar en Google
Banco de datos:
MEDLINE
Asunto principal:
Oligodendroglía
/
Calcio
/
Receptores de Ácido Kaínico
/
Receptores AMPA
Límite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Asunto de la revista:
NEUROLOGIA
Año:
2002
Tipo del documento:
Article
País de afiliación:
España