GABAA Receptor Expression in the Forebrain of Ataxic Rolling Nagoya Mice Journal Article

Authors: Nielsen, E. O.; Kaja, S.
Article Title: GABAA Receptor Expression in the Forebrain of Ataxic Rolling Nagoya Mice
Abstract: The human CACNA1A gene encodes the pore-forming alpha1 subunit 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 them Rolling Nagoya (tgrol), carrying the R1262G point mutation in the mouse Cacna1a gene. tgrol mice 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. gamma-Aminobutyric acid type A (GABAA) receptor subunit expression depends critically on neuronal calcium influx, and GABAA receptor dysfunction has previously been described for the cerebellum of tgrol and other ataxic Cacna1a mutant mice. Given the expression pattern of CaV2.1, it was hypothesized that calcium dysregulation in tgrol might affect GABAA receptor expression in the forebrain. Herein, functional GABAA receptors in the forebrain of tgrol mice were quantified and pharmacologically dissociated using [3H] radioligand binding. No gross changes to functional GABAA receptors were identified. Future cell type-specific analyses are required to identify possible cortical contributions to the psychomotor phenotype of tgrol mice.
Journal Title: Biology and medicine (Aligarh)
Volume: 6
Issue: 1
ISSN: 0974-8369
Publisher: Unknown  
Journal Place: India
Date Published: 2014
Start Page: 1000198
Language: ENG
Notes: LR: 20161025; GR: R01 GM102631/GM/NIGMS NIH HHS/United States; JID: 101524053; NIHMS630477; OTO: NOTNLM; ppublish