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

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*

*Corresponding author for this work
19 Citations (Scopus)


Summary 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. This study investigates detailed electrophysiological characteristics of hPSC-derived peripheral nociceptive neurons with focus on voltage-gated sodium channels. Besides the pain-relevant subtypes NAV1.8 and NAV1.9, Lampert, Winner, and colleagues find that significant amounts of the developmentally important NAV1.5 are expressed and functionally active. Thus, human hPSC-derived nociceptors offer a suitable model of developing sensory neurons.

Original languageEnglish
JournalStem Cell Reports
Issue number3
Pages (from-to)305-313
Number of pages9
Publication statusPublished - 08.09.2015


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