Reduction of P/Q-type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert-Eaton myasthenic syndrome.

Abstract

The aim of this study was to clarify whether autoimmunity against P/Q-type voltage-gated calcium channels (VGCCs) in the cerebellum was associated with the pathogenesis of paraneoplastic cerebellar degeneration (PCD) with Lambert-Eaton myasthenic syndrome (LEMS). We used human autopsy cerebellar tissues from three PCD-LEMS patients and six other disease patients including one with LEMS as the controls. We compared cerebellar P/Q-type VGCC in these patients and controls for the amount and ratio of autoantibody-channel complex using an 125I-omega-conotoxin MVIIC-binding assay with Scatchard analysis, and their distribution using autoradiography. The quantity of cerebellar P/Q-type VGCC measured by Scatchard analysis were reduced in PCD-LEMS patients (63.0 +/- 7.0 fmol/mg, n = 3), compared with the controls (297.8 +/- 38.9 fmol/mg, n = 6). The ratio of autoantibody-VGCC complexes to total P/Q-type VGCCs measured by immunoprecipitation assay were increased in PCD-LEMS patients. We analysed cerebellar specimens by autoradiography using (125)I-omega-conotoxin MVIIC, which specifically binds to P/Q-type VGCCs. In PCD-LEMS cerebellum, the toxin binding sites of P/Q-type VGCCs were markedly reduced compared with controls, especially in the molecular layer, which is the richest area of P/Q-type VGCCs in the normal cerebellum. This suggests that P/Q-type VGCCs of the cerebellar molecular layer is the immunological target in developing PCD-LEMS.

• Authors: Taku Fukuda, Masakatsu Motomura, Yoko Nakao, Hirokazu Shiraishi, Toshiro Yoshimura, Keisuke Iwanaga, Mitsuhiro Tsujihata, Katsumi Eguchi
• Journal: Annals of neurology (Ann Neurol) Vol. 53 Issue 1 Pg. 21-8 (Jan 2003) ISSN: 0364-5134 [Print] United States
• PMID: 12509844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Calcium Channels, N-Type
• Elapid Venoms
• Iodine Radioisotopes
• omega-Conotoxins
• voltage-dependent calcium channel (P-Q type)
• dendrotoxin

Topics

• Aged
• Autoantibodies (immunology)
• Autoradiography
• Calcium Channels, N-Type (immunology, metabolism)
• Cerebellar Ataxia (immunology, metabolism, pathology)
• Cerebellum (immunology, metabolism, pathology)
• Elapid Venoms (metabolism, pharmacology)
• Female
• Humans
• Iodine Radioisotopes
• Lambert-Eaton Myasthenic Syndrome (immunology, metabolism, pathology)
• Male
• Paraneoplastic Cerebellar Degeneration (immunology, metabolism, pathology)
• omega-Conotoxins (metabolism, pharmacology)