The Journal of Neurophysiology Vol. 80 No. 1 July 1998, pp. 297-308
Copyright ©1998 The American Physiological Society

Distinct GABA_B Actions Via Synaptic and Extrasynaptic Receptors in Rat Hippocampus In Vitro

Tri M. Pham, Suzanne Nurse, and Jean-Claude Lacaille

Département de Physiologie, Centre de Recherche en Sciences Neurologiques, Université de Montréal, Montreal, Quebec H3C 3J7, Canada

Pham, Tri M., Suzanne Nurse, and Jean-Claude Lacaille. Distinct GABA_B actions via synaptic and extrasynaptic receptors in rat hippocampus in vitro. J. Neurophysiol. 80: 297-308, 1998. Intracellular recordings were obtained from pyramidal cells to examine -aminobutyric acid-B (GABA_B)-mediated synaptic mechanisms in the CA1 region of rat hippocampal slices. To investigate if heterogeneous ionic mechanisms linked to GABA_B receptors originate from distinct sets of inhibitory fibers, GABA_B-mediated monosynaptic late inhibitory postsynaptic potentials (IPSPs) were elicited in the presence of antagonists of ionotropic glutamate and GABA_A 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 (E_rev) of late IPSPs was similar for all groups and close to the equilibrium potential of K⁺. Bath application of the GABA_B antagonist CGP55845A blocked all monosynaptic late IPSPs. During recordings with micropipettes containing guanosine-5'-O-(3-thiotriphosphate) (GTPS), the mean amplitude of all GABA_B 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 GABA_B-mediated hyperpolarizations elicited by local application of exogenous GABA only by ~50%. These results indicate that heterogenous K⁺ conductances activated by GABA_B 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 GABA_B mechanisms, giant GABA_B IPSPs were induced by 4-aminopyridine (4-AP) in the presence of antagonists of ionotropic glutamate and GABA_A receptors. The amplitude and time course 4-AP-induced late IPSPs were approximately double that of evoked monosynaptic late IPSPs, but their voltage sensitivity, E_rev, and antagonism by the GABA_B antagonist CGP55845A and intracellular GTPS were similar. Ba²⁺ completely abolished 4-AP-induced late IPSPs, whereas responses elicited by exogenous GABA were only reduced by ~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 GABA_B-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 GABA_B receptors, but that GABA released synaptically, either by electrical stimulation or 4-AP application, can only activate K⁺ conductances homogeneously sensitive to Ba²⁺. Thus GABA_B receptors located at synaptic and extrasynaptic sites on hippocampal pyramidal cells may be linked to distinct K⁺ conductances.

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