title: GABA(A)-dependent chloride influx modulates reversal potential of GABA(B)-mediated IPSPs in hippocampal pyramidal cells.
abstract: Changes in intracellular chloride concentration, mediated by chloride influx through GABA(A) receptor-gated channels, may modulate GABA(B) receptor-mediated inhibitory postsynaptic potentials (GABA(B) IPSPs) via unknown mechanisms. Recording from CA3 pyramidal cells in hippocampal slices, we investigated the impact of chloride influx during GABA(A) receptor-mediated IPSPs (GABA(A) IPSPs) on the properties of GABA(B) IPSPs. At relatively positive membrane potentials (near -55 mV), mossy fiber--evoked GABA(B) IPSPs were reduced (compared with their magnitude at -60 mV) when preceded by GABA(A) receptor--mediated chloride influx. This effect was not associated with a correlated reduction in membrane permeability during the GABA(B) IPSP. The mossy fiber--evoked GABA(B) IPSP showed a positive shift in reversal potential (from -99 to -93 mV) when it was preceded by a GABA(A) IPSP evoked at cell membrane potential of -55 mV as compared with -60 mV. Similarly, when intracellular chloride concentration was raised via chloride diffusion from an intracellular microelectrode, there was a reduction of the pharmacologically isolated monosynaptic GABA(B) IPSP and a concurrent shift of GABA(B) IPSP reversal potential from -98 to -90 mV. We conclude that in hippocampal pyramidal cells, in which "resting" membrane potential is near action potential threshold, chloride influx via GABA(A) IPSPs shifts the reversal potential of subsequent GABA(B) receptor--mediated postsynaptic responses in a positive direction and reduces their magnitude.
authors.affiliation: Department of Neurological Surgery, University of Washington, Seattle, Washington 98195-6470, USA.
authors.forename: V
authors.initials: V
authors.lastname: Lopantsev
authors.forename: P A
authors.initials: PA
authors.lastname: Schwartzkroin
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*
chemical_list: D002712:Chlorides; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C017069:bicuculline methiodide; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C066430:CGP 35348; D001640:Bicuculline