Referenced in: none

Automatically associated channels: Nav1.5

Title: Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors.

Authors: Esther Eberhardt, Steven Havlicek, Diana Schmidt, Andrea S Link, Cristian Neacsu, Zacharias Kohl, Martin Hampl, Andreas M Kist, Alexandra Klinger, Carla Nau, Jürgen Schüttler, Christian Alzheimer, Jürgen Winkler, Barbara Namer, Beate Winner, Angelika Lampert

Journal, date & volume: Stem Cell Reports, 2015 Sep 8 , 5, 305-13

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26321143

Abstract
Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain.