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

J. H. Ye, J. J. McArdle

Research output: Contribution to journalArticle

7 Scopus citations

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 - Oct 1995

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Keywords

  • 2
  • 3-butadione monoxine (BDM)
  • Glutamate receptor
  • hythalamic neuron
  • patch-clamp
  • phosphtase

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