title: GABAAReceptor Expression in the Forebrain of AtaxicRolling NagoyaMice.
abstract: The human CACNA1A gene encodes the pore-forming α1subunit of CaV2.1 (P/Q-type) calcium channels and is the locus for several neurological disorders, including episodic ataxia type 2 (EA2), spinocerebellar ataxia type 6 (SCA6) and Familial Hemiplegic Migraine type 1 (FHM1). Several spontaneous mouse Cacna1a mutant strains exist, among themRolling Nagoya(tgrol), carrying the R1262G point mutation in the mouse Cacna1a gene.tgrolmice display a phenotype of severe gait ataxia and motor dysfunction of the hind limbs. At the functional level, the R1262G mutation results in a positive shift of the activation voltage of the CaV2.1 channel and reduced current density. γ-Aminobutyric acid type A (GABAA) receptor subunit expression depends critically on neuronal calcium influx, and GABAAreceptor dysfunction has previously been described for the cerebellum oftgroland other ataxic Cacna1a mutant mice. Given the expression pattern of CaV2.1, it was hypothesized that calcium dysregulation intgrolmight affect GABAAreceptor expression in the forebrain. Herein, functional GABAAreceptors in the forebrain oftgrolmice were quantified and pharmacologically dissociated using [3H] radioligand binding. No gross changes to functional GABAAreceptors were identified. Future cell type-specific analyses are required to identify possible cortical contributions to the psychomotor phenotype oftgrolmice.
authors.affiliation: NeuroSearch A/S, Pederstrupvej 93, 2750 Ballerup, Denmark.
authors.forename: Elsebet Østergaard
authors.initials: EO
authors.lastname: Nielsen
authors.affiliation: NeuroSearch A/S, Pederstrupvej 93, 2750 Ballerup, Denmark ; School of Biological and Biomedical Sciences, Durham University, South Road, Science Laboratories, Durham DH1 3LE, United Kingdom ; Vision Research Center, Department of Ophthalmology University of Missouri, Kansas City, School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA ; K&P Scientific LLC, 8570 N Hickory St. Ste. 412, Kansas City, MO 64155, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Kaja
keywords: Ataxia; CaV2.1; Cacan1a; Calcium; Gamma aminobutyric receptor type A; Motor dysfunction; P/Q-type calcium channel; Pharmacology; Rolling Nagoya