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 mu M-5 mM) of ammonium chloride (NH4Cl) were investigated in rat hippocampal CA1 neurons. The amplitude of the evoked fast EPSPs decreased by NH4Cl in a concentration-dependent manner. The half-maximal inhibitory concentration for the inhibition of evoked fast EPSPs was 198 +/- 125 mu M (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 NH4Cl (200 mu M and 3 mM). The PPF ratio increased to 180 +/- 23% (n = 9) in the presence of 200 mu M NH4Cl compared with that in the absence of NH4Cl (142 +/- 24%, n = 9). In the presence of 3 mM NH4Cl, the PPF ratio increased to 172 +/- 30% (n = 7) compared with that in the absence of NH4Cl (126 +/- 13%, n = 7). This implies that NH4Cl suppressed the presynaptic release of glutamate. Exogenous glutamateor alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarization elicited by using pressure application did not reduce following superfusion with 200 mu M or 5 mM NH4Cl in the presence of 0.3 mu M tetrodotoxin, suggesting that NH4Cl 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 mu M NH4Cl but disappeared at 5 mM NH4Cl. The abolishment of action potentials in the presence of 5 mM NH4Cl was released by increasing the amplitude of the injection current. These results suggest that NH4Cl depresses evoked fast EPSPs mainly via a presynaptic mechanism at low NH4Cl concentrations, and the failure of action potential propagation through the excitatory nerve may also contribute to the depression of evoked fast EPSPs at high NH4Cl concentrations.