GABA_A-dependent chloride influx modulates reversal potential of GABA_B-mediated IPSPs in hippocampal pyramidal cells

Changes in intracellular chloride concentration, mediated by chloride influx through GABA_A receptor-gated channels, may modulate GABA_B receptor-mediated inhibitory postsynaptic potentials (GABA_B IPSPs) via unknown mechanisms. Recording from CA3 pyramidal cells in hippocampal slices, we investigated the impact of chloride influx during GABA_A receptor-mediated IPSPs (GABA_A IPSPs) on the properties of GABA_B IPSPs. At relatively positive membrane potentials (near -55 mV), mossy fiber-evoked GABA_B IPSPs were reduced (compared with their magnitude at -60 mV) when preceded by GABA_A receptor-mediated chloride influx. This effect was not associated with a correlated reduction in membrane permeability during the GABA_B IPSP. The mossy fiber-evoked GABA_B IPSP showed a positive shift in reversal potential (from -99 to -93 mV) when it was preceded by a GABA_A IPSP evoked at cell membrane potential of -55 mV as compared with -60 mV. Similarly, when intracellular chloride concentration was raised via chloride diffusion from an intracellular microelectrode, there was a reduction of the pharmacologically isolated monosynaptic GABA_B IPSP and a concurrent shift of GABA_B IPSP reversal potential from -98 to -90 mV. We conclude that in hippocampal pyramidal cells, in which "resting" membrane potential is near action potential threshold, chloride influx via GABA_A IPSPs shifts the reversal potential of subsequent GABA_B receptor-mediated postsynaptic responses in a positive direction and reduces their magnitude.