GABA_A receptors modulate the excitability of neurons by mediating IPSCs, but have also been shown to mediate a tonic current in cerebellar and hippocampal granule cells. We have recently reported that synaptic GABA_A receptors in interneurons and pyramidal cells of the CA1 region of the hippocampus show several pharmacological and biophysical differences (Semyanov & Kullmann, 2002). Here we report that GABA receptor-mediated tonic conductance also differs between the two cell types.

We obtained hippocampal slices from guinea-pigs killed by cervical dislocation. Whole-cell recordings were made either from interneurons (stratum radiatum or oriens) or from pyramidal cells in CA1. Spontaneous IPSCs (sIPSCs) were isolated by applying ionotropic glutamate and GABA_B receptor blockers. Because the pipette solution contained a high Cl^– concentration, both tonic and phasic GABA_A receptor-mediated currents were inward.

Perfusion of the broad spectrum GABA_A receptor antagonist picrotoxin (100 µM) abolished sIPSCs in both interneurons (n = 7) and pyramidal cells (n = 6). It also reduced the holding current in interneurons but not pyramidal cells, implying that a tonic conductance is only present in interneurons. Similar results were obtained with the GABA_A receptor antagonist bicuculline (10 µM, n = 4). Surprisingly, the holding current in interneurons was unaffected by 0.5 µM gabazine, even though this completely abolished sIPSCs (n = 6). Increasing the extracellular GABA concentration with the GABA transport inhibitor NO711 (20 µM), caused an increase in the GABA_A receptor-mediated tonic current in interneurons and also led to the appearance of a tonic current in pyramidal cells. This result suggests that differences in GABA transport may account for cell-type differences in tonic inhibition in the hippocampus.

Blockade of the tonic GABA_A receptor-mediated conductance led to an increased excitability of interneurons in response to current injection. This also resulted in an increased frequency of sIPSCs in pyramidal neurons.

The greater expression of tonic inhibition in interneurons may reflect a homeostatic role for this phenomenon: increases in extracellular GABA may render GABAergic cells relatively inexcitable, and therefore lead to a decrease in GABA release. This phenomenon may play an important role in regulating the excitability of the hippocampus.