title: Distinct GABAB actions via synaptic and extrasynaptic receptors in rat hippocampus in vitro.
abstract: Intracellular recordings were obtained from pyramidal cells to examine gamma-aminobutyric acid-B (GABAB)-mediated synaptic mechanisms in the CA1 region of rat hippocampal slices. To investigate if heterogeneous ionic mechanisms linked to GABAB receptors originate from distinct sets of inhibitory fibers, GABAB-mediated monosynaptic late inhibitory postsynaptic potentials (IPSPs) were elicited in the presence of antagonists of ionotropic glutamate and GABAA receptors and of an inhibitor of GABA uptake and were compared after direct stimulation of inhibitory fibers in three different CA1 layers: stratum oriens, radiatum, and lacunosum-moleculare. No significant differences were found in mean amplitude, rise time, or time to decay to half-amplitude of IPSPs evoked from the three layers. Mean equilibrium potential (Erev) of late IPSPs was similar for all groups and close to the equilibrium potential of K+. Bath application of the GABAB antagonist CGP55845A blocked all monosynaptic late IPSPs. During recordings with micropipettes containing guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS), the mean amplitude of all GABAB IPSPs gradually was reduced. Bath application of Ba2+ completely eliminated monosynaptic late IPSPs evoked from any of the stimulation sites. Late IPSPs were blocked completely during Ba2+ applications that reduced the GABAB-mediated hyperpolarizations elicited by local application of exogenous GABA only by approximately 50%. These results indicate that heterogenous K+ conductances activated by GABAB receptors do not originate from separate sets of inhibitory fibers in these layers. To examine if synchronous release of GABA from a larger number of inhibitory fibers could activate heterogeneous GABAB mechanisms, giant GABAB IPSPs were induced by 4-aminopyridine (4-AP) in the presence of antagonists of ionotropic glutamate and GABAA receptors. The amplitude and time course 4-AP-induced late IPSPs were approximately double that of evoked monosynaptic late IPSPs, but their voltage sensitivity, Erev, and antagonism by the GABAB antagonist CGP55845A and intracellular GTPgammaS were similar. Ba2+ completely abolished 4-AP-induced late IPSPs, whereas responses elicited by exogenous GABA were only reduced by approximately 50% in the same cells. These results indicate that synchronous activation of large numbers of inhibitory fibers, as induced by 4-AP, may not activate heterogenous GABAB-mediated conductances. Similarly, Ba2+ almost completely blocked late inhibitory postsynaptic currents evoked by stimulus trains. Overall, our results show that exogenous GABA can activate heterogenous K+ conductances via GABAB receptors, but that GABA released synaptically, either by electrical stimulation or 4-AP application, can only activate K+ conductances homogeneously sensitive to Ba2+. Thus GABAB receptors located at synaptic and extrasynaptic sites on hippocampal pyramidal cells may be linked to distinct K+ conductances.
authors.affiliation: Département de Physiologie, Centre de Recherche en Sciences Neurologiques, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
authors.forename: T M
authors.initials: TM
authors.lastname: Pham
authors.forename: S
authors.initials: S
authors.lastname: Nurse
authors.forename: J C
authors.initials: JC
authors.lastname: Lacaille
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D010721:Phosphinic Acids / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011712:Pyramidal Tracts / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D015221:Potassium Channels; D011412:Propanolamines; D018080:Receptors, GABA-B; C085075:CGP 55845A; D001464:Barium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015761:4-Aminopyridine