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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

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.

Authors+Show Affiliations

Departamento de Neurociencias, Universidad del País Vasco, Leioa, Vizcaya, Spain.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11895374

Citation

Alberdi, Elena, et al. "Ca(2+) Influx Through AMPA or Kainate Receptors Alone Is Sufficient to Initiate Excitotoxicity in Cultured Oligodendrocytes." Neurobiology of Disease, vol. 9, no. 2, 2002, pp. 234-43.
Alberdi E, Sánchez-Gómez MV, Marino A, et al. Ca(2+) influx through AMPA or kainate receptors alone is sufficient to initiate excitotoxicity in cultured oligodendrocytes. Neurobiol Dis. 2002;9(2):234-43.
Alberdi, E., Sánchez-Gómez, M. V., Marino, A., & Matute, C. (2002). Ca(2+) influx through AMPA or kainate receptors alone is sufficient to initiate excitotoxicity in cultured oligodendrocytes. Neurobiology of Disease, 9(2), 234-43.
Alberdi E, et al. Ca(2+) Influx Through AMPA or Kainate Receptors Alone Is Sufficient to Initiate Excitotoxicity in Cultured Oligodendrocytes. Neurobiol Dis. 2002;9(2):234-43. PubMed PMID: 11895374.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ca(2+) influx through AMPA or kainate receptors alone is sufficient to initiate excitotoxicity in cultured oligodendrocytes. AU - Alberdi,Elena, AU - Sánchez-Gómez,María Victoria, AU - Marino,Aida, AU - Matute,Carlos, PY - 2002/3/16/pubmed PY - 2002/5/10/medline PY - 2002/3/16/entrez SP - 234 EP - 43 JF - Neurobiology of disease JO - Neurobiol Dis VL - 9 IS - 2 N2 - 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. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/11895374/Ca_2+__influx_through_AMPA_or_kainate_receptors_alone_is_sufficient_to_initiate_excitotoxicity_in_cultured_oligodendrocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969996101904577 DB - PRIME DP - Unbound Medicine ER -