The influence of acidic media on the effect of beta-amyloid peptide on the function of glycine receptor in hippocampal neurons

- The effects of H+ on glycine-activated current (IGly) were studied using patch-clamp.
- Protons reduced the peak amplitude and accelerated the decay of IGly.
- The effects of H+ and beta-amyloid peptide (Aβ) on IGly were similar.
- Joint application of Aβ and H+ showed a mutual weakening of their action on IGly.

We have previously shown that application of beta-amyloid peptide 1-42 (Aβ) at picomolar/nanomolar concentrations caused a decrease in the peak amplitude and acceleration of desensitization of the glycine-activated chloride current (IGly) in hippocampal pyramidal neurons (Bukanova et al., 2016). The aim of this work was to study the effect of Aβ on IGly in an acidified medium. The relevance of this work is determined by the fact that the pathogenic effects of Aβ in Alzheimer's disease are usually accompanied by inflammatory processes and acidosis. The IGly was induced by 600 ms application of 100 μM (nearly EC50) or 500 μM (nearly saturating) glycine on isolated rat hippocampal neurons. The solution of glycine was neutral (pH 7.4) or acidic over a pH range of 5.0-7.0. It was found that 600 ms application of protons rapidly, reversibly and in dose-dependent manner decreased the peak amplitude and accelerated the desensitization of IGly. The effect of H+ on IGly desensitization did not depend on glycine concentration and may be considered noncompetitive, while the effect on IGly peak disappeared at saturating glycine concentration and can be regarded as a competitive. These characteristics of the proton effects on IGly coincide with the characteristics of the Aβ effects on IGly. Experiments with joint application of Aβ and H+ showed interdependence of their effects. Addition of Aβ to perfusing solution reduced H+ effects on IGly while long pretreatment of Aβ with acid solution prevented the effects of the peptide on IGly. Our results suggest the existence of common sites for Aβ and H+ on the GlyR and indicate a mutual weakening of the inhibitory action of these molecules on IGly.