Differential cerebellar GABAA receptor expression in mice with mutations in CaV2.1 (P/Q-type) calcium channels.

摘要: Abstract Ataxia is the predominant clinical manifestation of cerebellar dysfunction. Mutations in human CACNA1A gene, encoding pore-forming α 1 subunit Ca V 2.1 (P/Q-type) calcium channels, underlie several neurological disorders, including Episodic type 2 and Familial Hemiplegic Migraine (FHM1). Several mouse mutants exist that harbor mutations orthologous Cacna1a gene. The spontaneous Rolling Nagoya ( tg rol ), Tottering ) Leaner ln mice exhibit behavioral motor phenotypes, ataxia. Transgenic knock-in (KI) strains with FHM1 R192Q S218L missense have been generated. KI are non-ataxic, whereas display a complex phenotype includes Given dependence γ-aminobutyric acid A (GABA receptor functioning on localized currents, functional link between GABAergic inhibition ataxia, we hypothesized GABA expression differentially affected contributes to ataxic phenotype. Herein quantified receptors pharmacologically dissociated mutants. We did not identify differences subunits or number non-ataxic strain. In contrast, had ∼15% decrease receptors, showed ∼29% increase. Our data suggest differential changes profile may contribute ataxia targeting might represent feasible complementary strategy treat