Frontiers in Neurology (Jul 2017)

Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype

  • Barbara Namer,
  • Barbara Namer,
  • Kirstin Ørstavik,
  • Roland Schmidt,
  • Norbert Mair,
  • Inge Petter Kleggetveit,
  • Maximillian Zeidler,
  • Theresa Martha,
  • Ellen Jorum,
  • Ellen Jorum,
  • Martin Schmelz,
  • Theodora Kalpachidou,
  • Michaela Kress,
  • Michiel Langeslag

DOI
https://doi.org/10.3389/fneur.2017.00335
Journal volume & issue
Vol. 8

Abstract

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The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0). The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons.

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