title: Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors.
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: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany; Department of Anesthesiology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
authors: Esther
authors: E
authors: Eberhardt
authors: IZKF Junior Research Group and BMBF Research Group Neuroscience, IZKF, Friedrich-Alexander-Universität Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
authors: Steven
authors: S
authors: Havlicek
authors: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany; IZKF Junior Research Group and BMBF Research Group Neuroscience, IZKF, Friedrich-Alexander-Universität Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
authors: Diana
authors: D
authors: Schmidt
authors: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany.
authors: Andrea S
authors: AS
authors: Link
authors: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany.
authors: Cristian
authors: C
authors: Neacsu
authors: Department of Molecular Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany.
authors: Zacharias
authors: Z
authors: Kohl
authors: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany; Institute of Physiology, Uniklinik RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors: Martin
authors: M
authors: Hampl
authors: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany.
authors: Andreas M
authors: AM
authors: Kist
authors: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany.
authors: Alexandra
authors: A
authors: Klinger
authors: Department of Anesthesiology and Intensive Care, University Medical Center Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
authors: Carla
authors: C
authors: Nau
authors: Department of Anesthesiology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
authors: Jürgen
authors: J
authors: Schüttler
authors: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany.
authors: Christian
authors: C
authors: Alzheimer
authors: Department of Molecular Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany.
authors: Jürgen
authors: J
authors: Winkler
authors: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany.
authors: Barbara
authors: B
authors: Namer
authors: IZKF Junior Research Group and BMBF Research Group Neuroscience, IZKF, Friedrich-Alexander-Universität Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany. Electronic address: beate.winner@med.uni-erlangen.de.
authors: Beate
authors: B
authors: Winner
authors: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany; Institute of Physiology, Uniklinik RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. Electronic address: alampert@ukaachen.de.
authors: Angelika
authors: A
authors: Lampert
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D015640:Ion Channel Gating; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009619:Nociceptors / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D013779:Tetrodotoxin
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D013779:Tetrodotoxin