Developmental regulation of human embryonic stem cell-derived neurons by calcium entry via transient receptor potential channels

Jason P. Weick, Michael Johnson, Su Chun Zhang

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Spontaneous calcium (Ca2+) transients in the developing nervous system can affect proliferation, migration, neuronal subtype specification, and neurite outgrowth. Here, we show that telencephalic human neuroepithelia (hNE) and postmitotic neurons (PMNs) generated from embryonic stem cells display robust Ca2+ transients. Unlike previous reports in animal models, transients occurred by a Gd3+/La3+-sensitive, but thapsigargin- and Cd2+-insensitive, mechanism, strongly suggestive of a role for transient receptor potential (Trp) channels. Furthermore, Ca 2+ transients in PMNs exhibited an additional sensitivity to the canonical Trp (TrpC) antagonist SKF96365 and shRNA-mediated knockdown of the TrpC1 subunit. Functionally, inhibition of Ca21 transients in dividing hNE cells led to a significant reduction in proliferation, whereas either pharmacological inhibition or shRNA-mediated knockdown of the TrpC1 and TrpC4 subunits significantly reduced neurite extension in PMNs. Primary neurons cultured from fetal human cortex displayed nearly identical Ca2+ transients and pharmacological sensitivities to Trp channel antagonists. Together these data suggest that Trp channels present a novel mechanism for controlling Ca 2+ transients in human neurons and may offer a target for regulating proliferation and neurite outgrowth when engineering cells for therapeutic transplantation.

Original languageEnglish (US)
Pages (from-to)2906-2916
Number of pages11
JournalStem Cells
Volume27
Issue number12
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

Keywords

  • Embryonic stem cells
  • TrpC1
  • TrpC4
  • Voltage-gated calcium channels

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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