title: Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells.
abstract: Using intracellular recording techniques in CA1 cells in the hippocampal slice, we studied the responses of cells to synaptically released and iontophoretically applied GABA. With high-resistance, Cl(-)-filled electrodes, which inverted and enlarged the responses at normal resting potentials, we examined spontaneous GABA-mediated IPSPs. Usually we recorded the spontaneous events in the presence of carbachol (10-25 microM), which significantly increased IPSP frequency and blocked potentially confounding K+ conductances. Following a train of action potentials, spontaneous IPSPs were transiently suppressed. This suppression could not be accounted for by membrane conductance changes following the train or activation of a recurrent circuit. Whole-cell voltage-clamp recordings in the slice indicated that the amplitudes of the spontaneous GABAA inhibitory postsynaptic currents (IPSCs) were also diminished following the action potential train. In some cases BAY K 8644, a Ca2+ channel agonist, enhanced the suppression of IPSPs, while buffering changes in [Ca2+]i with EGTA or BAPTA prevented it. The monosynaptically evoked IPSC in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dl-2-amino-5-phosphonovaleric acid (APN) was also diminished following a train of action potentials; however, iontophoretically applied GABA responses did not change significantly. These studies suggest that localized physiological changes in postsynaptic [Ca2+]i potently modulate synaptic GABAA inputs and that this modulation may be an important regulatory mechanism in mammalian brain.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
authors.forename: T A
authors.initials: TA
authors.lastname: Pitler
authors.forename: B E
authors.initials: BE
authors.lastname: Alger
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051381:Rats; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D002118:Calcium