Somatostatin depresses excitatory but not inhibitory neurotransmission in rat CA1 hippocampus

被引:91
作者
Tallent, MK [1 ]
Siggins, GR [1 ]
机构
[1] Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA
关键词
D O I
10.1152/jn.1997.78.6.3008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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-methyl-isoxazole-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 mu M had no direct effects on either gamma-aminobutyric acid-A (GABA(A)) or GABA(B) 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 G(i)/G(o) 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.
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页码:3008 / 3018
页数:11
相关论文
共 67 条
[1]   A-G PROTEIN COUPLES SEROTONIN AND GABA-B RECEPTORS TO THE SAME CHANNELS IN HIPPOCAMPUS [J].
ANDRADE, R ;
MALENKA, RC ;
NICOLL, RA .
SCIENCE, 1986, 234 (4781) :1261-1265
[2]   EVIDENCE THAT SOMATOSTATIN ENHANCES ENDOGENOUS ACETYLCHOLINE-RELEASE IN THE RAT HIPPOCAMPUS [J].
ARAUJO, DM ;
LAPCHAK, PA ;
COLLIER, B ;
QUIRION, R .
JOURNAL OF NEUROCHEMISTRY, 1990, 55 (05) :1546-1555
[3]  
Boehm S, 1997, J NEUROSCI, V17, P4066
[4]  
BRAZEAU P, 1972, SCIENCE, V129, P77
[5]  
BREDER CD, 1992, J NEUROSCI, V12, P3920
[6]  
Choi S, 1996, J NEUROSCI, V16, P36
[7]   ELECTROPHYSIOLOGICAL EVIDENCE FROM GLUTAMATE MICROAPPLICATIONS FOR LOCAL EXCITATORY CIRCUITS IN THE CA1 AREA OF RAT HIPPOCAMPAL SLICES [J].
CHRISTIAN, EP ;
DUDEK, FE .
JOURNAL OF NEUROPHYSIOLOGY, 1988, 59 (01) :110-123
[8]   PRESYNAPTIC INHIBITION BY NEUROPEPTIDE-Y AND BACLOFEN IN HIPPOCAMPUS - INSENSITIVITY TO PERTUSSIS TOXIN TREATMENT [J].
COLMERS, WF ;
PITTMAN, QJ .
BRAIN RESEARCH, 1989, 498 (01) :99-104
[9]  
COLMERS WF, 1993, PRESYNAPTIC RECEPTOR, P87