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

Effects of NH4Cl on CA1 pyramidal neurons and synaptic transmission we re investigated with intracellular recording in fully submerged rat hi ppocampal 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 repolarizati on, without significant change in membrane conductance. When membrane potential was returned to control level by the injection of a steady o utward current, action potential amplitude recovered but repolarizatio n remained slow. The extent of depolarization was not dependent on the concentration of NH4Cl between 1 and 4 mM. NH4Cl greatly depressed or thodromic transmission evoked by the stimulation of Schaffer collatera l/commissural fibers several minutes after depolarizing the CA1 neuron . Interruption of transmission began with a decrease in excitatory pos tsynaptic potential (EPSP) amplitude and eventually EPSPs were almost eliminated. When NK4Cl was removed, it took 2-3 min for membrane poten tial and 10-15 min for transmission to recover. Inward currents induce d by bath application of quisqualate acting on alpha-amino-3-hydroxy-5 -methyl-4-isoxazole propionic acid (AMPA) receptors were also depresse d. In contrast, NH4Cl enhanced N-methyl-D-aspartate (NMDA)-induced cur rents. This potentiation disappeared in the absence of added Mg2+. A r eduction in quisqualate-induced responses provided a possible explanat ion for the inhibition of excitatory transmission by NH4Cl.