Cav2.1 voltage-dependent Ca 2+ channel current is inhibited by serum from select patients with guillain-barré syndrome

Yoshihiko Nakatani, Sayako Hotta, Iku Utsunomiya, Keiko Tanaka, Keiko Hoshi, Toshi Ariga, Robert K Yu, Tadashi Miyatake, Kyoji Taguchi

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

To investigate the pathophysiological mechanisms of immune-mediated peripheral neuropathies, we studied the effects of sera from patients with Guillain-Barré syndrome (GBS) on the Cav2.1 voltage-dependent calcium channel (VDCC) current in Purkinje cells. Using the whole-cell recording technique, Cav2.1 VDCC current was measured in cerebellar Purkinje cells in the presence of serum from GBS patients with acute motor axonal neuropathy (AMAN) or acute inflammatory demyelinating polyneuropathy (AIDP). The AMAN patient sera significantly inhibited the Cav2.1 VDCC current compared with healthy volunteer sera, and this inhibition was fully reversible by washing out the AMAN serum. Similarly, IgG purified from AMAN sera also inhibited the Cav2.1 VDCC current. However, the activation and inactivation kinetics of the Cav2.1 VDCC currents were not affected by serum from an AMAN patient. Moreover, the VDCC current of Purkinje cells was also inhibited by IgG anti-GM1 monoclonal antibody (anti-GM1 mAb). In an immunocytochemical study using double fluorescence staining, Purkinje cells were stained by monoclonal IgG anti-GM1 mAb. In contrast, AIDP patient and healthy volunteer sera did not affect the Cav2.1 VDCC current. These results suggest that in some case of GBS, particularly of AMAN patients with IgG anti-GM1 mAb, muscle weakness may be induced by dysfunction of Cav2.1 VDCC functioning at the motor nerve terminals.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalNeurochemical Research
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Acute inflammatory demyelinating polyneuropathy
  • Acute motor axonal neuropathy
  • Cav2.1(P/Q-type) voltage-dependent calcium channels
  • Guillain-Barré syndrome
  • IgG anti-GM1 monoclonal antibody

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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