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Ca2+-permeable non-NMDA glutamate receptors in rat magnocellular basal forebrain neurones.
J Physiol. 1998 Apr 15; 508 (Pt 2):453-69.JP

Abstract

1. Ionotropic glutamate receptor-mediated responses were recorded from rat magnocellular basal forebrain neurones under voltage clamp from a somatically located patch-clamp pipette. Currents were recorded from both acutely dissociated neurones and neurones maintained in culture for up to 6 weeks. 2. Non-NMDA and NMDA receptor-mediated events could be distinguished pharmacologically using the selective agonists (S)-alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA), and antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D(-)-2-amino-5-phosphonopentanoic acid (AP5). 3. Responses to rapid application of AMPA displayed pronounced and rapid desensitization. Responses to kainate showed no desensitization. Steady-state EC50 values for AMPA and kainate were 2.7 +/- 0.4 microM (n = 5) and 138 +/- 25 microM (n = 10), respectively. Cyclothiazide markedly increased current amplitude of responses to both agonists, whereas concanavalin A had no clear effect on either response. The selective AMPA receptor antagonist GYKI 53655 inhibited responses to kainate with an IC50 of 1.2 +/- 0.08 microM (n = 5) at -70 mV. These data strongly suggest that AMPA receptors are the predominant non-NMDA receptors expressed by basal forebrain neurones. 4. At -70 mV, approximately 6 % of control current amplitude remained, at a maximally effective concentration of GYKI 53655. This residual response displayed desensitization, was insensitive to cyclothiazide and was potentiated by concanavalin A, suggesting that it was mediated by a kainate receptor. 5. Current-voltage relationships for non-NMDA receptor-mediated currents were obtained from both nucleated patches pulled from neurones in culture and from acutely dissociated neurones. With 30 microM spermine in the recording pipette, currents frequently displayed double-rectification characteristic of non-NMDA receptors with high Ca2+ permeabilities. Ca2+ permeability, relative to Na+ and Cs+, was investigated using constant field theory. The measured Ca2+ to Na+ permeability coefficient ratio was 0.26-3.6; median, 1.27 (n = 15). 6. Current flow through non-NMDA receptors was inhibited by Ca2+, Cd2+ and Co2+ ions. At a holding potential of -70 mV, a maximally effective concentration of Cd2+ (> 30 mM) reduced current amplitude by approximately 90 %, with an IC50 of 44 microM. In six out of seven cells tested, block by Cd2+ was voltage sensitive. 7. Ca2+ permeability of many of the non-NMDA receptors expressed by magnocellular basal forebrain neurones may underlie the unusual sensitivity of cholinergic basal forebrain neurones to non-NMDA receptor-mediated excitotoxicity.

Authors+Show Affiliations

Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. jwaters@leland.stanford.eduNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9508809

Citation

Waters, D J., and T G. Allen. "Ca2+-permeable non-NMDA Glutamate Receptors in Rat Magnocellular Basal Forebrain Neurones." The Journal of Physiology, vol. 508 (Pt 2), 1998, pp. 453-69.
Waters DJ, Allen TG. Ca2+-permeable non-NMDA glutamate receptors in rat magnocellular basal forebrain neurones. J Physiol (Lond). 1998;508 (Pt 2):453-69.
Waters, D. J., & Allen, T. G. (1998). Ca2+-permeable non-NMDA glutamate receptors in rat magnocellular basal forebrain neurones. The Journal of Physiology, 508 (Pt 2), 453-69.
Waters DJ, Allen TG. Ca2+-permeable non-NMDA Glutamate Receptors in Rat Magnocellular Basal Forebrain Neurones. J Physiol (Lond). 1998 Apr 15;508 (Pt 2):453-69. PubMed PMID: 9508809.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ca2+-permeable non-NMDA glutamate receptors in rat magnocellular basal forebrain neurones. AU - Waters,D J, AU - Allen,T G, PY - 1998/5/22/pubmed PY - 1998/5/22/medline PY - 1998/5/22/entrez SP - 453 EP - 69 JF - The Journal of physiology JO - J. Physiol. (Lond.) VL - 508 (Pt 2) N2 - 1. Ionotropic glutamate receptor-mediated responses were recorded from rat magnocellular basal forebrain neurones under voltage clamp from a somatically located patch-clamp pipette. Currents were recorded from both acutely dissociated neurones and neurones maintained in culture for up to 6 weeks. 2. Non-NMDA and NMDA receptor-mediated events could be distinguished pharmacologically using the selective agonists (S)-alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA), and antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D(-)-2-amino-5-phosphonopentanoic acid (AP5). 3. Responses to rapid application of AMPA displayed pronounced and rapid desensitization. Responses to kainate showed no desensitization. Steady-state EC50 values for AMPA and kainate were 2.7 +/- 0.4 microM (n = 5) and 138 +/- 25 microM (n = 10), respectively. Cyclothiazide markedly increased current amplitude of responses to both agonists, whereas concanavalin A had no clear effect on either response. The selective AMPA receptor antagonist GYKI 53655 inhibited responses to kainate with an IC50 of 1.2 +/- 0.08 microM (n = 5) at -70 mV. These data strongly suggest that AMPA receptors are the predominant non-NMDA receptors expressed by basal forebrain neurones. 4. At -70 mV, approximately 6 % of control current amplitude remained, at a maximally effective concentration of GYKI 53655. This residual response displayed desensitization, was insensitive to cyclothiazide and was potentiated by concanavalin A, suggesting that it was mediated by a kainate receptor. 5. Current-voltage relationships for non-NMDA receptor-mediated currents were obtained from both nucleated patches pulled from neurones in culture and from acutely dissociated neurones. With 30 microM spermine in the recording pipette, currents frequently displayed double-rectification characteristic of non-NMDA receptors with high Ca2+ permeabilities. Ca2+ permeability, relative to Na+ and Cs+, was investigated using constant field theory. The measured Ca2+ to Na+ permeability coefficient ratio was 0.26-3.6; median, 1.27 (n = 15). 6. Current flow through non-NMDA receptors was inhibited by Ca2+, Cd2+ and Co2+ ions. At a holding potential of -70 mV, a maximally effective concentration of Cd2+ (> 30 mM) reduced current amplitude by approximately 90 %, with an IC50 of 44 microM. In six out of seven cells tested, block by Cd2+ was voltage sensitive. 7. Ca2+ permeability of many of the non-NMDA receptors expressed by magnocellular basal forebrain neurones may underlie the unusual sensitivity of cholinergic basal forebrain neurones to non-NMDA receptor-mediated excitotoxicity. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/9508809/Ca2+_permeable_non_NMDA_glutamate_receptors_in_rat_magnocellular_basal_forebrain_neurones_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3751&date=1998&volume=508&spage=453 DB - PRIME DP - Unbound Medicine ER -