PubMed 18687887

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav2.1

Title: Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels.

Authors: Kei Watase, Curtis F Barrett, Taisuke Miyazaki, Taro Ishiguro, Kinya Ishikawa, Yuanxin Hu, Toshinori Unno, Yaling Sun, Sayumi Kasai, Masahiko Watanabe, Christopher M Gomez, Hidehiro Mizusawa, Richard W Tsien, Huda Y Zoghbi

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2008 Aug 19 , 105, 11987-92

PubMed link:

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disorder caused by CAG repeat expansions within the voltage-gated calcium (Ca(V)) 2.1 channel gene. It remains controversial whether the mutation exerts neurotoxicity by changing the function of Ca(V)2.1 channel or through a gain-of-function mechanism associated with accumulation of the expanded polyglutamine protein. We generated three strains of knockin (KI) mice carrying normal, expanded, or hyperexpanded CAG repeat tracts in the Cacna1a locus. The mice expressing hyperexpanded polyglutamine (Sca6(84Q)) developed progressive motor impairment and aggregation of mutant Ca(V)2.1 channels. Electrophysiological analysis of cerebellar Purkinje cells revealed similar Ca(2+) channel current density among the three KI models. Neither voltage sensitivity of activation nor inactivation was altered in the Sca6(84Q) neurons, suggesting that expanded CAG repeat per se does not affect the intrinsic electrophysiological properties of the channels. The pathogenesis of SCA6 is apparently linked to an age-dependent process accompanied by accumulation of mutant Ca(V)2.1 channels.