title: Somatostatin depresses excitatory but not inhibitory neurotransmission in rat CA1 hippocampus.
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)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate and N-methyl--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 microM had no direct effects on either gamma-aminobutyric acid-A (GABAA) or GABAB receptor-mediated inhibitory postsynaptic currents (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 seizurelike 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.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Tallent
authors.forename: G R
authors.initials: GR
authors.lastname: Siggins
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D019204:GTP-Binding Proteins / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D019204:GTP-Binding Proteins; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D018092:Kainic Acid Receptors; D013004:Somatostatin