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

• Published in: Neuropharmacology 1995-10, Vol.34 (10), p.1259-1272
• Main Authors: Ye, J.-H., McArdle, J.J.
• Format: Article
• Language: English
• Subjects: 3-butadione monoxine (BDM); Animals; Biological and medical sciences; Cholinesterase Reactivators - pharmacology; Diacetyl - analogs & derivatives; Diacetyl - pharmacology; Excitatory Amino Acids - pharmacology; Fundamental and applied biological sciences. Psychology; Glutamate receptor; Glutamic Acid - pharmacology; Hypothalamus - drug effects; hythalamic neuron; Isolated neuron and nerve. Neuroglia; Kainic Acid - pharmacology; Membrane Potentials - drug effects; Mice; Mice, Inbred Strains; N-Methylaspartate - pharmacology; patch-clamp; Patch-Clamp Techniques; phosphtase; Vertebrates: nervous system and sense organs
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/0028-3908(95)00100-K

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.