Ammonium prepulse: effects on intracellular pH and bioelectric activity of CA3-neurones in guinea pig hippocampal slices

The ammonium prepulse technique was used to study influences of intracellular pH (pH(i)) on bioelectric activity of CA3-neurones in hippocampal slices. 60, 180 or 600 s lasting NH4Cl (10 mM) pulses led to a transient intracellular alkalosis (Delta pH(i): up to 0.2 pH-units) in about one-half of the neurones loaded with 2',7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein-acetoxymethylester (BCECF-AM). No alkalosis was seen in the remainder cells. The amount of alkalosis depended on the actual pH(i) of each neurone and increased when the pH(i) decreased. Washout of NH4Cl induced a fall in pH(i) (Delta pH(i): 0.12-0.54 pH-units) which recovered within < 20 min. Frequency of spontaneous action potentials remained unchanged during washin of ammonium (60 or 180 s). However, pre-treatment with low concentrations of bicuculline-methiodide (0.01 mu M) or caffeine (0.1 mM), both of which did not change bioelectric activity per se, permitted a burst-activity to occur during ammonium-washin in about one-half of the neurones. In all neurones, washout of ammonium inhibited spontaneous and epileptiform activity (elicited by 1 mM caffeine, 20-50 mu M bicuculline-methiodide, or 50-75 mu M 4-aminopyridine) for less than or equal to 20 min. This inhibition was accompanied by an increased membrane conductance (up to 20%) and a hyperpolarisation of up to 10 mV. We conclude that intracellular alkalosis augments, whereas intracellular acidosis depresses bioelectric activity of CA3-neurones. (C) 1999 Elsevier Science B.V. All rights reserved.