Effects of ammonium ions on spontaneous action potentials and on contents of sodium, potassium, ammonium and chloride ions in brain in vitro

The effects of ammonium ions on the frequency of spontaneous action potentials in guinea-pig cerebellar slices, recorded with an extracellular microelectrode, and on the contents of sodium, potassium and chloride ions in incubated guinea-pig cerebellar, and rat brain cortex, slices have been investigated. The frequencies of the spontaneous action potentials are partially suppressed by concentrations of NH₄Cl less than 2 mm and completely abolished by concentrations exceeding 2 mm . The amplitudes of the spike discharges are unaffected. A lag period of at least 15 s precedes the inhibition. The suppressing action of NH on the spike frequency is reversible, as shown by complete recovery on removal of NH after short time intervals. Deficiency of Cl^? in the superfusion medium causes conversion of inhibition by NH to excitation. Reduction of K⁺], or of Na⁺], causes increase of inhibition by NH in a normal Cl¹], and reduction of excitation in a low Cl¹], medium. The inhibitory effects of NH on spike frequency are unaffected by picrotoxin or strychnine. NH₄Cl, even at 1 or 2 mm , causes a significant increase of aerobic glycolysis. It is suggested that the lag period preceding the suppression of the frequency of spike discharges by NH is partly due to a metabolic change induced by NH, perhaps a transient lowering of pH in the responsible neurons, causing changed permeability to Cl^? and possibly to K⁺ and Na⁺, NH promotes, in guinea-pig cerebellar slices, an inward flow of Na⁺ and an outward flow of K⁺, the latter being greater than that due to exchange of K⁺ for NH. NH₄Cl at 1 or 2 mm causes an outward flow of K⁺ and an inward flow of Cl^? in rat brain cortex slices. The movement of Cl^? is biphasic, the first phase, seen with low NH], consisting of an increase of tissue content of Cl^? with little or no fluid uptake and a second phase, seen with high (> 5 mm ) concentrations of NH, in which the uptake of Cl^? is directly proportional to the fluid uptake. It is suggested that the first phase is largely neuronal in location whilst the second is largely glial. In infant rat brain cortex slices, there seems to be predominantly an equal exchange of NH for K^+. There is little evidence of energy assisted concentrative uptake of NH by brain slices and this is thought to be due largely to the rapid diffusion of undissociated NH₃ across cell membranes. It is suggested that some NH (amounting to about 2 mequiv/1) may be bound in the brain. It is concluded that changes in ionic permeabilities, particularly that of Cl^?, partly due to a metabolic action, may be responsible for some of the acute cerebral effects of NH administration.