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

Eberhardt E, Havlicek S, Schmidt D, Link A, Neacsu C, Kohl Z, Hampl M, Kist A, Klinger A, Nau C, Schüttler J, Alzheimer C, Winkler J, Namer B, Winner B, Lampert A (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Stem Cell Reports Elsevier

Book Volume: 5

Pages Range: 305-13

Journal Issue: 3

DOI: 10.1016/j.stemcr.2015.07.010

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.

Authors with CRIS profile

Esther Eberhardt Lehrstuhl für Physiologie Steven Havlicek Department of Molecular Neurology Diana Schmidt Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 3 Prof. Dr. Winner Andrea Link Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung Cristian Neacsu Institut für Physiologie und Pathophysiologie Zacharias Kohl Department of Molecular Neurology Martin Hampl Lehrstuhl für Physiologie Andreas Kist Lehrstuhl für Physiologie Alexandra Klinger Institut für Physiologie und Pathophysiologie Jürgen Schüttler Lehrstuhl für Anästhesiologie Christian Alzheimer Lehrstuhl für Physiologie Jürgen Winkler Professur für Molekulare Neurologie Barbara Namer Lehrstuhl für Physiologie Beate Winner Professur für Stammzell-Modelle seltener neuraler Erkrankungen Angelika Lampert Lehrstuhl für Physiologie

Involved external institutions

Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE)

How to cite

APA:

Eberhardt, E., Havlicek, S., Schmidt, D., Link, A., Neacsu, C., Kohl, Z.,... Lampert, A. (2015). Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors. Stem Cell Reports, 5(3), 305-13. https://doi.org/10.1016/j.stemcr.2015.07.010

MLA:

Eberhardt, Esther, et al. "Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors." Stem Cell Reports 5.3 (2015): 305-13.

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