Human Hyperekplexic Mutations in Glycine Receptors Disinhibit the Brainstem by Hijacking GABA_A Receptors.

ABSTRACT: Hyperekplexia disease is usually caused by naturally occurring point mutations in glycine receptors (GlyRs). However, the γ-aminobutyric acid type A receptor (GABA_AR) seems to be also involved regarding the therapeutic basis for hyperekplexia using benzodiazepines, which target GABA_ARs but not GlyRs. Here, we show that the function of GABA_ARs was significantly impaired in the hypoglossal nucleus of hyperekplexic transgenic mice. Such impairment appeared to be mediated by interaction between GABA_AR and mutant GlyR. The GABA_AR dysfunction was caused only by mutant GlyR consisting of homomeric α₁ subunits, which locate primarily at pre- and extra-synaptic sites. In addition, the rescue effects of diazepam were attenuated by Xli

SUBMITTER: Zou G 

PROVIDER: S-EPMC6715904 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature