Excitatory amino acid induced currents of isolated murine hypothalamic neurons and their suppression by 2,3-butanedione monoxime

Jiang Ye, J. J. McArdle

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Ionic currents induced by excitatory amino acids were investigated for freshly isolated murine hypothalamic neurons with whole cell recording techniques. L-glutamate or N-methyl-D-aspartate (NMDA), in combination with glycine, resulted in a rapidly rising current which decayed in the continued presence of agonist. In contrast, kainate currents did not decay. While quisqualate-induced current maintained a steady amplitude in the continued presence of agonist, a rapid decay phase appeared at holding potentials negative to - 50 mV. Co-application of 2,3-butanedione monoxime (BDM) reversibly inhibited the currents due to each agonist. Detailed study of BDM suppression of kainate-induced current revealed two components. A component with a rapid onset did not involve phosphatase action since 500 μMATP-γ-S or a protein kinase inhibitor (H-7, 200 μM) did not alter current suppression or recovery after BDM. Thus, the probable mechanism for this component of BDM 's effect is direct block of the kainate-activated ion channel. However, preincubating neurons with 30 mM BDM reduced their subsequent response to kainate alone. This persistent effect of BDM was not seen for neurons dialyzed with a solution containing ATP-γ-S during conventional whole cell recording. Furthermore, exposure to H-7 prevented recovery of the kainate response suppressed by preincubation in BDM. These findings suggest that BDM causes sustained suppression of the kainate response of hypothalamic neurons via a "chemical phosphatase" action.

Original languageEnglish (US)
Pages (from-to)1259-1272
Number of pages14
JournalNeuropharmacology
Volume34
Issue number10
DOIs
StatePublished - Jan 1 1995

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Excitatory Amino Acids
Kainic Acid
Neurons
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Patch-Clamp Techniques
Phosphoric Monoester Hydrolases
Quisqualic Acid
Pharmacologic Actions
diacetylmonoxime
N-Methylaspartate
Protein Kinase Inhibitors
Ion Channels
Glycine
Glutamic Acid
Adenosine Triphosphate

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

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title = "Excitatory amino acid induced currents of isolated murine hypothalamic neurons and their suppression by 2,3-butanedione monoxime",
abstract = "Ionic currents induced by excitatory amino acids were investigated for freshly isolated murine hypothalamic neurons with whole cell recording techniques. L-glutamate or N-methyl-D-aspartate (NMDA), in combination with glycine, resulted in a rapidly rising current which decayed in the continued presence of agonist. In contrast, kainate currents did not decay. While quisqualate-induced current maintained a steady amplitude in the continued presence of agonist, a rapid decay phase appeared at holding potentials negative to - 50 mV. Co-application of 2,3-butanedione monoxime (BDM) reversibly inhibited the currents due to each agonist. Detailed study of BDM suppression of kainate-induced current revealed two components. A component with a rapid onset did not involve phosphatase action since 500 μMATP-γ-S or a protein kinase inhibitor (H-7, 200 μM) did not alter current suppression or recovery after BDM. Thus, the probable mechanism for this component of BDM 's effect is direct block of the kainate-activated ion channel. However, preincubating neurons with 30 mM BDM reduced their subsequent response to kainate alone. This persistent effect of BDM was not seen for neurons dialyzed with a solution containing ATP-γ-S during conventional whole cell recording. Furthermore, exposure to H-7 prevented recovery of the kainate response suppressed by preincubation in BDM. These findings suggest that BDM causes sustained suppression of the kainate response of hypothalamic neurons via a {"}chemical phosphatase{"} action.",
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Excitatory amino acid induced currents of isolated murine hypothalamic neurons and their suppression by 2,3-butanedione monoxime. / Ye, Jiang; McArdle, J. J.

In: Neuropharmacology, Vol. 34, No. 10, 01.01.1995, p. 1259-1272.

Research output: Contribution to journalArticle

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