EFFECTS OF AMMONIUM-IONS ON SYNAPTIC TRANSMISSION AND ON RESPONSES TO QUISQUALATE AND N-METHYL-D-ASPARTATE IN HIPPOCAMPAL CA1 PYRAMIDAL NEURONS IN-VITRO

Effects of NH4Cl on CA1 pyramidal neurons and synaptic transmission were investigated with intracellular recording in fully submerged rat hippocampal slices. Superfusion with 1-4 mM NH4Cl reversibly depolarized the membrane by 15.1 +/- 1.4 mV, reduced the amplitude and broadened the duration of action potentials due to a slower rate of repolarization, without significant change in membrane conductance. When membrane potential was returned to control level by the injection of a steady outward current, action potential amplitude recovered but repolarization remained slow. The extent of depolarization was not dependent on the concentration of NH4Cl between 1 and 4 mM. NH4Cl greatly depressed orthodromic transmission evoked by the stimulation of Schaffer collateral/commissural fibers several minutes after depolarizing the CA1 neuron. Interruption of transmission began with a decrease in excitatory postsynaptic potential (EPSP) amplitude and eventually EPSPs were almost eliminated. When NK4Cl was removed, it took 2-3 min for membrane potential and 10-15 min for transmission to recover. Inward currents induced by bath application of quisqualate acting on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors were also depressed. In contrast, NH4Cl enhanced N-methyl-D-aspartate (NMDA)-induced currents. This potentiation disappeared in the absence of added Mg2+. A reduction in quisqualate-induced responses provided a possible explanation for the inhibition of excitatory transmission by NH4Cl.