Excitatory amino acid induced currents of isolated murine hypothalamic neurons and their suppression by 2,3-butanedione monoxime.
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 microM ATP-gamma-S or a protein kinase inhibitor (H-7, 200 microM) 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-gamma-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.
Ye
J H
JH
Department of Anesthesiology, New Jersey Medical School (UMDNJ), Newark 07103-2714, USA.
McArdle
J J
JJ
D000818:Animals; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology; D018408:Patch-Clamp Techniques
D002801:Cholinesterase Reactivators; D018846:Excitatory Amino Acids; C004717:diacetylmonoxime; D018698:Glutamic Acid; D016202:N-Methylaspartate; D003931:Diacetyl; D007608:Kainic Acid