Actions of somatostatin on GABA-ergic synaptic transmission in the CA1 area of the hippocampus.
Somatostatin and gamma-aminobutyric acid (GABA) are co-localized in some neurons in the CA1 area of the hippocampus. Since it is possible that the peptide and the amino acid are co-released, the interactions between the actions of somatostatin and GABA-ergic inhibitory post-synaptic potentials (IPSPs) in the CA1 pyramidal neurons of guinea pig hippocampal slices have been investigated. Somatostatin (2 microM) induced a hyperpolarization of the CA1 neurons associated with a reduction in the input resistance of the cells. These effects were not blocked by picrotoxinin (20 microM) or phaclofen (1 mM). Chelation of intracellular Ca2+ (Ca2+i) with BAPTA or the inhibition of protein kinase C (PKC) with sphingosine (30 microM) had no significant effects on the hyperpolarizing actions of somatostatin. The peptide suppressed the GABAA receptor-mediated fast IPSPs and the GABAB receptor-mediated slow IPSPs, but had no significant effect on the excitatory post-synaptic potentials (EPSPs). Somatostatin-induced depression of the IPSPs was not due to the hyperpolarization of the neurons. Baclofen (20 microM) suppressed the EPSP, as well as the fast and the slow IPSPs. The hyperpolarization of the CA1 neurons caused by somatostatin was greatly reduced in the presence of baclofen, an effect that was not due to the hyperpolarization of the cell by baclofen. The presence of QX-314 in the CA1 neurons, which suppressed the Na+ spikes and the slow IPSPs, prevented the hyperpolarization of the neurons by somatostatin and baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
Sastry
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D000818:Animals; D002118:Calcium / Q000502:physiology; D005071:Evoked Potentials / Q000502:physiology; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects; D013004:Somatostatin / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; C012647:QX-314; D013004:Somatostatin; D008012:Lidocaine; D011493:Protein Kinase C; D002118:Calcium