SOMATOSTATIN DEPRESSES EXCITATORY BUT NOT INHIBITORY NEUROTRANSMISSION IN RAT CA1 HIPPOCAMPUS. Melanie K. Tallent and George R. Siggins,. Department of Neuropharmacology, The Scripps Research Institute La Jolla, CA 92037.
APStracts 4:218N, 1997.
ABSTRACT
In rat CA1 hippocampal pyramidal neurons (HPNs), somatostatin (SST) has inhibitory postsynaptic actions, including hyperpolarization of the membrane at rest and augmentation of the K+ M-current. However, the effects of SST on synaptic transmission in this brain region have not been well-characterized. Therefore, we used intracellular voltage-clamp recordings in rat hippocampal slices to assess the effects of SST on pharmacologically-isolated synaptic currents in HPNs. SST depressed both (R,S)-a-amino-3-hydroxy-5- methylisoxazole-4-propionic acid (AMPA)/kainate and N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents (EPSCs) in a reversible manner, with an apparent IC50 of 22 nM and a maximal effect at 100 nM. In contrast, SST at concentrations up to 5 mM had no direct effects on either GABAA or GABAB receptor-mediated IPSCs. The depression of EPSCs by SST was especially robust during hyperexcited states when polysynaptic EPSCs were present, suggesting that this peptide could play a compensatory role during seizure-like activity. SST effects were greatly attenuated by the alkylating agent N-ethylmaleimide, thus implicating a transduction mechanism involving the Gi/Go family of G-proteins. Use of 2 M Cs+ in the recording electrode blocked the postsynaptic modulation of K+ currents by SST, but did not alter the effects of SST on EPSCs, indicating that postsynaptic K+ currents are not involved in this action of SST. However, 2 mM external Ba2+ blocked the effect of SST on EPSCs, suggesting that presynaptic K+ channels or other presynaptic mechanisms may be involved. These findings and previous results from our laboratory show that SST has multiple inhibitory effects in hippocampus. 

Received 5 May 1997; accepted in final form 28 August 1997.
APS Manuscript Number J362-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 5 September 1997