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Pharmacological characterization of a GluR6 kainate receptor in cultured hippocampal neurons.
Eur J Pharmacol. 1999 Aug 13; 378(3):331-7.EJ

Abstract

We have examined the pharmacology of kainate receptors in cultured hippocampal neurons (6-8 days in vitro (DIV)) from embryonic rats (E17). Cultured neurons were pre-treated with concanavalin A to remove kainate receptor desensitization and whole-cell voltage clamp electrophysiology employed to record inward currents in response to glutamatergic agonists and antagonists. N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor responses were blocked using MK801 (3 microM) and the 2,3-benzodiazepine, LY300168 (GYKI53655, 50 microM), respectively. Inward currents were recorded in hippocampal neurons upon application of kainate and the 2S,4R isomer of 4-methyl glutamic acid (SYM2081) with EC50 values of 3.4 +/- 0.4 microM and 1.6 +/- 0.5 microM, respectively (n = 6 cells). The GluR5 selective agonists, LY339434 (100 microM) and (RS)-2-amino-3-(3-hydroxy-5-tert-butyl-4-isoxazolyl) propionic acid (ATPA) (100 microM), did not evoke detectable inward currents in any cell responding to kainate. LY293558 and the selective GluR5 antagonist, LY382884, had weak antagonist effects on responses evoked by either kainate or (2S,4R)-4-methyl glutamate (IC50 > 300 microM). The quinoxalinedione, 2,3-dihyro-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), blocked both kainate and (2S,4R)-4-methyl glutamate-activated currents at much lower concentrations (IC50 approximately 10 microM). These results provide pharmacological evidence that ion channels comprised of GluR6 kainate receptor subunits mediate kainate receptor responses in hippocampal neurons cultured 6-8 DIV.

Authors+Show Affiliations

Eli Lilly and Company, Lilly Neuroscience, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285-0510, USA. bleakman_david@lilly.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10493110

Citation

Bleakman, D, et al. "Pharmacological Characterization of a GluR6 Kainate Receptor in Cultured Hippocampal Neurons." European Journal of Pharmacology, vol. 378, no. 3, 1999, pp. 331-7.
Bleakman D, Ogden AM, Ornstein PL, et al. Pharmacological characterization of a GluR6 kainate receptor in cultured hippocampal neurons. Eur J Pharmacol. 1999;378(3):331-7.
Bleakman, D., Ogden, A. M., Ornstein, P. L., & Hoo, K. (1999). Pharmacological characterization of a GluR6 kainate receptor in cultured hippocampal neurons. European Journal of Pharmacology, 378(3), 331-7.
Bleakman D, et al. Pharmacological Characterization of a GluR6 Kainate Receptor in Cultured Hippocampal Neurons. Eur J Pharmacol. 1999 Aug 13;378(3):331-7. PubMed PMID: 10493110.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological characterization of a GluR6 kainate receptor in cultured hippocampal neurons. AU - Bleakman,D, AU - Ogden,A M, AU - Ornstein,P L, AU - Hoo,K, PY - 1999/9/24/pubmed PY - 1999/9/24/medline PY - 1999/9/24/entrez SP - 331 EP - 7 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 378 IS - 3 N2 - We have examined the pharmacology of kainate receptors in cultured hippocampal neurons (6-8 days in vitro (DIV)) from embryonic rats (E17). Cultured neurons were pre-treated with concanavalin A to remove kainate receptor desensitization and whole-cell voltage clamp electrophysiology employed to record inward currents in response to glutamatergic agonists and antagonists. N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor responses were blocked using MK801 (3 microM) and the 2,3-benzodiazepine, LY300168 (GYKI53655, 50 microM), respectively. Inward currents were recorded in hippocampal neurons upon application of kainate and the 2S,4R isomer of 4-methyl glutamic acid (SYM2081) with EC50 values of 3.4 +/- 0.4 microM and 1.6 +/- 0.5 microM, respectively (n = 6 cells). The GluR5 selective agonists, LY339434 (100 microM) and (RS)-2-amino-3-(3-hydroxy-5-tert-butyl-4-isoxazolyl) propionic acid (ATPA) (100 microM), did not evoke detectable inward currents in any cell responding to kainate. LY293558 and the selective GluR5 antagonist, LY382884, had weak antagonist effects on responses evoked by either kainate or (2S,4R)-4-methyl glutamate (IC50 > 300 microM). The quinoxalinedione, 2,3-dihyro-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), blocked both kainate and (2S,4R)-4-methyl glutamate-activated currents at much lower concentrations (IC50 approximately 10 microM). These results provide pharmacological evidence that ion channels comprised of GluR6 kainate receptor subunits mediate kainate receptor responses in hippocampal neurons cultured 6-8 DIV. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/10493110/Pharmacological_characterization_of_a_GluR6_kainate_receptor_in_cultured_hippocampal_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(99)00478-1 DB - PRIME DP - Unbound Medicine ER -