Research reportFunctional modulation of strychnine-sensitive glycine receptors in rat hippocampal pyramidal neurons by amyloid-β protein (1-42)

- Aβ42 modulates glycine receptors in pyramidal hippocampal neurons.
- Aβ in picomolar concentrations accelerates the desensitization of glycine current.
- Aβ reversibly suppress the peak amplitude of glycine current.
- Currents activated by taurine and β-alanine have similar sensitivity to Aβ.
- Bath Aβ application suppresses the amplitude of glycine current.

Amyloid-β peptide (Aβ) is considered a key protein in the pathogenesis of Alzheimer's disease because of its neurotoxicity, resulting in impaired synaptic function and memory. On the other hand, it was demonstrated that low (picomolar) concentrations of Aβ enhance synaptic plasticity and memory, suggesting that in the healthy brain, physiological Aβ concentrations are necessary for normal cognitive functions. In the present study, we found that Aβ (1−42) in concentrations of 10 pМ - 100 nМ enhanced desensitization of the glycine-activated current in isolated CA3 pyramidal neurons and also reversibly suppressed its peak amplitude during short (600 ms) co-application with agonist. The effect was most prominent at low glycine concentrations. When glycine receptors were activated by other receptor agonists - taurine and β-alanine, the changes of current kinetics and amplitudes induced by Aβ had a similar character. When Aβ (100 pM) was added to the bath solution, it caused, besides acceleration of desensitization, more pronounced reduction of peak current amplitude. This effect developed slowly, during a few minutes, and was more prominent at saturating concentrations of agonists. The results suggest that Aβ interacts with glycine receptors through three different mechanisms - by enhancing receptor desensitization, by rapid inhibition of the receptor, and also by means of a slowly developing inhibition of the amplitude of the current, possibly through intracellular mechanisms. The observed changes in the activity of glycine receptors induced by Aβ can lead to suppression of the tonic inhibition of hippocampal neurons mediated by extrasynaptic glycine receptors.