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

Cited 61 time in webofscience Cited 0 time in scopus
  • Hit : 70
  • Download : 0
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.
Publisher
ELSEVIER IRELAND LTD
Issue Date
2015-05
Language
English
Article Type
Article
Citation

NEUROSCIENCE LETTERS, v.594, pp.163 - 168

ISSN
0304-3940
DOI
10.1016/j.neulet.2015.01.084
URI
http://hdl.handle.net/10203/305034
Appears in Collection
BC-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 61 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0