Properties of human Cav2.1 channel with a spinocerebellar ataxia type 6 mutation expressed in Purkinje cells

Hironao Saegusa, Minoru Wakamori, Yoshihiro Matsuda, Junyang Wang, Yasuo Mori, Shuqin Zong, Tsutomu Tanabe

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Spinocerebellar ataxia type 6 (SCA6) is caused by polyglutamine expansion in P/Q-type Ca2+ channels (Cav2.1) and is characterized by predominant degeneration of cerebellar Purkinje cells. To characterize the Cav2.1 channel with an SCA6 mutation in cerebellar Purkinje cells, we have generated knock-in mouse models that express human Cav2.1 with 28 polyglutamine repeats (disease range) and with 13 polyglutamine repeats (normal range). Patch-clamp recordings of the Purkinje cells from homozygous control or SCA6 knock-in mice revealed a non-inactivating current that is highly sensitive to a spider toxin ω-Agatoxin IVA, indicating that the human Cav2.1 expressed in Purkinje cells exhibits typical P-type properties in contrast to the previous data showing Q-type properties, when it was expressed in cultured cell lines. Furthermore, the voltage dependence of activation and inactivation and current density were not different between SCA6 and control, though these properties were altered in previous reports using non-neuronal cells as expression systems. Therefore, our results do not support the notion that the alteration of the channel properties may underlie the pathogenic mechanism of SCA6.

Original languageEnglish
Pages (from-to)261-270
Number of pages10
JournalMolecular and Cellular Neuroscience
Volume34
Issue number2
DOIs
Publication statusPublished - 2007 Feb

Keywords

  • Ca2.1 channel
  • Knock-in mice
  • P-type current
  • Purkinje cells
  • Spinocerebellar ataxia type 6

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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