The inhibition of evoked excitatory postsynaptic potentials produced by ammonium chloride in rat hippocampal CA1 neurons.

The depression of evoked fast excitatory postsynaptic potentials (EPSPs) following superfusion with various concentrations (3 μM-5 mM) of ammonium chloride (NHCl) were investigated in rat hippocampal CA1 neurons. The amplitude of the evoked fast EPSPs decreased by NHCl in a concentration-dependent manner. The half-maximal inhibitory concentration for the inhibition of evoked fast EPSPs was 198 ± 125 μM (n = 8). The facilitation of a pair of field EPSPs elicited by paired-pulse stimulation (40-ms interval) (paired-pulse facilitation, PPF) was recorded following superfusion with NHCl (200 μM and 3 mM). The PPF ratio increased to 180 ± 23% (n = 9) in the presence of 200 μM NHCl compared with that in the absence of NHCl (142 ± 24%, n = 9). In the presence of 3 mM NHCl, the PPF ratio increased to 172 ± 30% (n = 7) compared with that in the absence of NHCl (126 ± 13%, n = 7). This implies that NHCl suppressed the presynaptic release of glutamate. Exogenous glutamate- or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarization elicited by using pressure application did not reduce following superfusion with 200 μM or 5 mM NHCl in the presence of 0.3 μM tetrodotoxin, suggesting that NHCl did not affect the postsynaptic glutamate response. Action potentials elicited by rectangular outward current injection from CA3 neurons projecting to CA1 neurons were persistent at 200 μM NHCl but disappeared at 5 mM NHCl. The abolishment of action potentials in the presence of 5 mM NHCl was released by increasing the amplitude of the injection current. These results suggest that NHCl depresses evoked fast EPSPs mainly via a presynaptic mechanism at low NHCl concentrations, and the failure of action potential propagation through the excitatory nerve may also contribute to the depression of evoked fast EPSPs at high NHCl concentrations.