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Ca(2+)-permeable AMPA receptors and selective vulnerability of motor neurons.
J Neurol Sci. 2000 Nov 01; 180(1-2):29-34.JN

Abstract

To evaluate the role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis (ALS), we compared the sensitivity of motor neurons and that of dorsal horn neurons to kainic acid (KA). Short exposure to KA resulted in the death of motor neurons, while dorsal horn neurons were unaffected. This selective motor neuron death was completely dependent on extracellular Ca(2+) and insensitive to inhibitors of voltage-operated Ca(2+) or Na(+) channels. It was also completely inhibited by the specific AMPA antagonist LY300164 and by Joro spider toxin (JSTx), a selective blocker of AMPA receptors that lack the edited GluR2 subunit. KA selectively killed those motor neurons that stained positive for the Co(2+) histochemical staining, a measure for the presence of Ca(2+)-permeable AMPA receptors. These results suggest that Ca(2+) entry via Ca(2+)-permeable AMPA receptors is responsible for the selective motor neuron death. As the Ca(2+) permeability of the AMPA receptor is regulated by its GluR2 subunit, we stained motor neurons for GluR2. Immunoreactivity was present in all motor neurons, albeit to a variable degree. However, double-staining experiments demonstrated that motor neurons clearly expressing GluR2, also expressed Ca(2+)-permeable AMPA receptors. This indicates that despite the abundant expression of GluR2, this subunit is excluded from a subset of AMPA receptors and that the activation of these receptors is responsible for the selective motor neuron death.

Authors+Show Affiliations

Laboratory of Neurobiology, Department of Neurology, University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Ludo.Vandenbosch@med.kuleuven.ac.beNo affiliation info availableNo 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

11090861

Citation

Van Den Bosch, L, et al. "Ca(2+)-permeable AMPA Receptors and Selective Vulnerability of Motor Neurons." Journal of the Neurological Sciences, vol. 180, no. 1-2, 2000, pp. 29-34.
Van Den Bosch L, Vandenberghe W, Klaassen H, et al. Ca(2+)-permeable AMPA receptors and selective vulnerability of motor neurons. J Neurol Sci. 2000;180(1-2):29-34.
Van Den Bosch, L., Vandenberghe, W., Klaassen, H., Van Houtte, E., & Robberecht, W. (2000). Ca(2+)-permeable AMPA receptors and selective vulnerability of motor neurons. Journal of the Neurological Sciences, 180(1-2), 29-34.
Van Den Bosch L, et al. Ca(2+)-permeable AMPA Receptors and Selective Vulnerability of Motor Neurons. J Neurol Sci. 2000 Nov 1;180(1-2):29-34. PubMed PMID: 11090861.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ca(2+)-permeable AMPA receptors and selective vulnerability of motor neurons. AU - Van Den Bosch,L, AU - Vandenberghe,W, AU - Klaassen,H, AU - Van Houtte,E, AU - Robberecht,W, PY - 2000/11/25/pubmed PY - 2001/2/28/medline PY - 2000/11/25/entrez SP - 29 EP - 34 JF - Journal of the neurological sciences JO - J Neurol Sci VL - 180 IS - 1-2 N2 - To evaluate the role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis (ALS), we compared the sensitivity of motor neurons and that of dorsal horn neurons to kainic acid (KA). Short exposure to KA resulted in the death of motor neurons, while dorsal horn neurons were unaffected. This selective motor neuron death was completely dependent on extracellular Ca(2+) and insensitive to inhibitors of voltage-operated Ca(2+) or Na(+) channels. It was also completely inhibited by the specific AMPA antagonist LY300164 and by Joro spider toxin (JSTx), a selective blocker of AMPA receptors that lack the edited GluR2 subunit. KA selectively killed those motor neurons that stained positive for the Co(2+) histochemical staining, a measure for the presence of Ca(2+)-permeable AMPA receptors. These results suggest that Ca(2+) entry via Ca(2+)-permeable AMPA receptors is responsible for the selective motor neuron death. As the Ca(2+) permeability of the AMPA receptor is regulated by its GluR2 subunit, we stained motor neurons for GluR2. Immunoreactivity was present in all motor neurons, albeit to a variable degree. However, double-staining experiments demonstrated that motor neurons clearly expressing GluR2, also expressed Ca(2+)-permeable AMPA receptors. This indicates that despite the abundant expression of GluR2, this subunit is excluded from a subset of AMPA receptors and that the activation of these receptors is responsible for the selective motor neuron death. SN - 0022-510X UR - https://www.unboundmedicine.com/medline/citation/11090861/Ca_2+__permeable_AMPA_receptors_and_selective_vulnerability_of_motor_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-510X(00)00414-7 DB - PRIME DP - Unbound Medicine ER -