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 influ x through GABA(A) receptor-gated channels, may modulate GABA(B) receptor-me diated inhibitory postsynaptic potentials (GABA(B) IPSPs) via unknown mecha nisms. Recording from CA3 pyramidal cells in hippocampal slices, we investi gated the impact of chloride influx during GABA(B) receptor-mediated IPSPs (GABA(A) IPSPs) on the properties of GABA IPSPs. At relatively positive mem brane potentials (near -55 mV), mossy fiber-evoked GABA(B) IPSPs were reduc ed (compared with their magnitude at -60 mV) when preceded by GABA(A) recep tor-mediated chloride influx. This effect was not associated with a correla ted reduction in membrane permeability during the GABA(B) IPSP. The mossy f iber-evoked GABA(B) IPSP showed a positive shift in reversal potential (fro m -99 to -93 mV) when it was preceded by a GABA(A) IPSP evoked at cell memb rane potential of -55 mV as compared with -60 mV. Similarly, when intracell ular chloride concentration was raised via chloride diffusion from an intra cellular microelectrode, there was a reduction of the pharmacologically iso lated monosynaptic GABA(B) IPSP and a concurrent shift of GABA(B) IPSP reve rsal potential from -98 to -90 mV. We conclude that in hippocampal pyramida l cells, in which "resting" membrane potential is near action potential thr eshold, chloride influx via GABA(B) IPSPs shifts the reversal potential of subsequent GABA(B) receptor-mediated postsynaptic responses in a positive d irection and reduces their magnitude.