Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells.
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.
Pitler
T A
TA
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
Alger
B E
BE
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*
D005680:gamma-Aminobutyric Acid; D002118:Calcium