title: A spontaneous tonic chloride conductance in solitary glutamatergic hippocampal neurons.
abstract: GABA-A receptors mediate both phasic synaptic inhibition and more recently appreciated tonic currents in the vertebrate central nervous system. We addressed discrepancies in the literature regarding the pharmacology of tonic currents by examining tonic currents in a controlled environment of dissociated, solitary glutamatergic neurons. We describe a novel tonically active, bicuculline-sensitive chloride conductance that is insensitive to gabazine and to picrotoxin and thus not mediated by conventional GABA receptors. We exclude a significant contribution from small conductance calcium-gated potassium (SK) channels. We also pharmacologically exclude calcium-gated chloride channels, glycine receptors and the chloride current associated with glutamate transport. Finally, we demonstrate that, although small, this current modulates neuronal excitability. We speculate that this tonic current may provide a complementary mechanism for the regulation of neuronal excitability, particularly in regions with low ambient GABA concentrations. We conclude that this bicuculline-sensitive conductance needs to be accounted for in studies of GABA tonic currents, lest it be confused with currents associated with GABA overflow.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA. LEisenman@wustl.edu
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Eisenman
authors.forename: Geraldine
authors.initials: G
authors.lastname: Kress
authors.forename: Charles F
authors.initials: CF
authors.lastname: Zorumski
authors.forename: Steven
authors.initials: S
authors.lastname: Mennerick
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D001640:Bicuculline; D018118:Chloride Channels; D018756:GABA Antagonists; D018698:Glutamic Acid; D010852:Picrotoxin; D011724:Pyridazines; D011963:Receptors, GABA-A; D051640:Small-Conductance Calcium-Activated Potassium Channels; C049853:gabazine