The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain

NEUROSCIENCE LETTERS

卷:594

Article

Choi, L.¹  Vernon, J.¹  Kopach, O.¹  Mitlett, M. S.¹  Mills, K.¹  Clayton, P. T.¹  Meert, T.¹  Wood, J. N.^1,2 

[1] UCL, Wolfson Inst Biomed Res, Mol Nocicept Grp, London WC1E 6BT, England

[2] Seoul Natl Univ, Dept Mol Med, Programme BK21, Seoul 151, South Korea

关键词: Pain;    Calcium imaging;    Voltage-dependent Ca2+ channels;    Fabry disease;    Dorsal root ganglia;   

DOI  :  10.1016/j.neulet.2015.01.084

来源: Elsevier

【 摘 要 】

Fabry disease is an X-linked lysosomal storage disorder characterised by accumulation of glycosphin-golipids, and accompanied by clinical manifestations, such as cardiac disorders, renal failure, pain and peripheral neuropathy. Globotriaosylsphingosine (lyso-Gb3), a deacylated form of globotriaosylceramide (Gb3), has emerged as a marker of Fabry disease. We investigated the link between Gb3, lyso-Gb3 and pain. Plantar administration of lyso-Gb3 or Gb3 caused mechanical allodynia in healthy mice. In vitro application of 100 nM lyso-Gb3 caused uptake of extracellular calcium in 10% of sensory neurons expressing nociceptor markers, rising to 40% of neurons at 1 mu M, a concentration that may occur in Fabry disease patients. Peak current densities of voltage-dependent Ca2+ channels were substantially enhanced by application of 1 mu M lyso-Gb3. These studies suggest a direct role for lyso-Gb3 in the sensitisation of peripheral nociceptive neurons that may provide an opportunity for therapeutic intervention in the treatment of Fabry disease-associated pain. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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