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 NH4Cl 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.
Fan
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Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
Szerb
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JC
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D011810:Quinoxalines; D000643:Ammonium Chloride; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016318:Quisqualic Acid; D008274:Magnesium