Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death-preventing effect of Ca V2.1 Ca 2+ channela - Loss-of-function cellular model of SCA6

Zenjiro Matsuyama, Naomi Kimoto Yanagisawa, Yoko Aoki, John L. Black, Vanda A. Lennon, Yasuo Mori, Keiji Imoto, Takashi Inuzuka

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Spinocerebellar ataxia (SCA) 6 is caused by small expansion of a polyglutamine sequence, encoded by CAG trinucleotide repeats, at the C-terminal end of the human Ca V2.1 (P/Q-type) Ca 2+ channel α 12.1 subunit and it manifests itself as slowly progressive cerebellar ataxia. To elucidate the pathogenic mechanisms underlying SCA6, we introduced CAG repeats of various lengths into the Ca 2+ channel α 12.1 subunit cDNA and expressed them in baby hamster kidney cells stably expressing the auxiliary subunits (α 2δ and β 4). The occurrence of cell death differed between cells transfected with the normal and mutant Ca 2+ channels under the condition of serum starvation plus potassium-induced depolarization, and Cdk inhibition elucidated the differences more clearly. The Ca V2.1 (P/Q-type) Ca 2+ channel-specific blocker ω-agatoxin IVA abolished the cell-death-preventing effect of the normal Ca 2+ channel. Together with our previous finding that the polyglutamine expansion in SCA6 interferes with the Ca 2+ channel to reduce Ca 2+ influx, these results indicate that impaired function of the mutant Ca 2+ channels rendered them unable to prevent cell death.

Original languageEnglish (US)
Pages (from-to)198-204
Number of pages7
JournalNeurobiology of Disease
Volume17
Issue number2
DOIs
StatePublished - Nov 1 2004

Keywords

  • Apoptosis
  • Ca 2.1 Ca channel
  • Depolarization
  • Polyglutamine
  • SCA6

ASJC Scopus subject areas

  • Neurology

Fingerprint Dive into the research topics of 'Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death-preventing effect of Ca <sub>V</sub>2.1 Ca <sup>2+</sup> channela - Loss-of-function cellular model of SCA6'. Together they form a unique fingerprint.

  • Cite this