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Use-dependent inhibition of glycine-activated chloride current in rat neurons by &bgr;-amyloid peptide pretreated with hexafluoroisopropanol

Hexafluoroisopropanol (HFIP) is a nonpolar organic solvent that is often used to prepare &bgr;-amyloid peptide (A&bgr;) samples. In this work, we compare the effects of two different species derived from… Click to show full abstract

Hexafluoroisopropanol (HFIP) is a nonpolar organic solvent that is often used to prepare &bgr;-amyloid peptide (A&bgr;) samples. In this work, we compare the effects of two different species derived from synthetic A&bgr;1–42 and prepared without HFIP (A&bgr;) or using HFIP (A&bgr;/HFIP) on the glycine-activated chloride current (IGly). The experiments were conducted on the pyramidal neurons isolated from CA3 region of rat hippocampus. Transmembrane currents were recorded using a conventional patch-clamp technique in the whole-cell configuration. The IGly was induced by a step application of the agonist for 600 ms through glass capillary. A&bgr; or A&bgr;/HFIP was coapplied with glycine. The effects of the two species of the peptide have similar and distinctive features. Both substances caused a reduction in the peak amplitude and an acceleration of desensitization of the IGly. At the same time, the effect of A&bgr;/HFIP was found to develop and recover more slowly and required several repeated applications for its saturation (use dependence). The effect of A&bgr;/HFIP was voltage independent and equally pronounced at negative and positive membrane potentials. First, our results confirm that HFIP pretreatment may influence the properties of A&bgr;. Second, new information on the glycine receptor ability to interact with drugs in use-dependent mode was obtained.

Keywords: hfip; bgr; amyloid peptide; bgr hfip; bgr amyloid; glycine

Journal Title: NeuroReport
Year Published: 2017

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