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

被引：42

作者：

Eberhardt, Esther ^{[1
,2
]}

Havlicek, Steven ^{[3
,4
]}

Schmidt, Diana ^{[1
,3
,4
]}

Link, Andrea S. ^{[1
]}

Neacsu, Cristian ^{[1
]}

Kohl, Zacharias ^{[5
]}

Hampl, Martin ^{[1
,6
]}

Kist, Andreas M. ^{[1
]}

Klinger, Alexandra ^{[1
]}

Nau, Carla ^{[7
]}

Schuettler, Juergen ^{[2
]}

Alzheimer, Christian ^{[1
]}

Winkler, Juergen ^{[5
]}

Namer, Barbara ^{[1
]}

Winner, Beate ^{[3
,4
]}

Lampert, Angelika ^{[1
,6
]}

机构：

[1] Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, D-91054 Erlangen, Germany

[2] Univ Erlangen Nurnberg, Dept Anesthesiol, Univ Klinikum Erlangen, D-91054 Erlangen, Germany

[3] Univ Erlangen Nurnberg, IZKF, IZKF Jr Res Grp, D-91054 Erlangen, Germany

[4] Univ Erlangen Nurnberg, IZKF, BMBF Res Grp Neurosci, D-91054 Erlangen, Germany

[5] Univ Erlangen Nurnberg, Dept Mol Neurol, Univ Klinikum Erlangen, D-91054 Erlangen, Germany

[6] Uniklin RWTH Aachen, Inst Physiol, D-52074 Aachen, Germany

[7] Univ Med Ctr Schleswig Holstein, Dept Anesthesiol & Intens Care, D-23538 Lubeck, Germany

来源：

STEM CELL REPORTS | 2015年 / 5卷 / 03期

关键词：

PLURIPOTENT STEM-CELLS; SENSORY NEURONS; PAIN; EXPRESSION;

D O I：

10.1016/j.stemcr.2015.07.010

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：305 / 313

页数：9

共 3 条

[1] TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors
Jonas, Robin
Prato, Vincenzo
Lechner, Stefan G.
Groen, Gerbrand
Obreja, Otilia
Werland, Fiona
Rukwied, Roman
Klusch, Andreas
Petersen, Marlen
Carr, Richard W.
Schmelz, Martin
FRONTIERS IN CELLULAR NEUROSCIENCE, 2020, 14
[2] Selected Ionotropic Receptors and Voltage-Gated Ion Channels: More Functional Competence for Human Induced Pluripotent Stem Cell (iPSC)-Derived Nociceptors
Schoepf, Clemens L.
Zeidler, Maximilian
Spiecker, Lisa
Kern, Georg
Lechner, Judith
Kummer, Kai K.
Kress, Michaela
BRAIN SCIENCES, 2020, 10 (06)
[3] Developmental expression of the TTX-resistant voltage-gated sodium channels Nav1.8 (SNS) and Nav1.9 (SNS2) in primary sensory neurons
Benn, SC
Costigan, M
Tate, S
Fitzgerald, M
Woolf, CJ
JOURNAL OF NEUROSCIENCE, 2001, 21 (16) : 6077 - 6085

← 1 →