Extremely low-frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Ca(v)1-channel activity

J Cell Physiol. 2008 Apr;215(1):129-39. doi: 10.1002/jcp.21293.


We previously reported that exposure to extremely low-frequency electromagnetic fields (ELFEFs) increases the expression and function of voltage-gated Ca2+)channels and that Ca2+ influx through Ca(v)1 channels plays a key role in promoting the neuronal differentiation of neural stem/progenitor cells (NSCs). The present study was conducted to determine whether ELFEFs influence the neuronal differentiation of NSCs isolated from the brain cortices of newborn mice by modulating Ca(v)1-channel function. In cultures of differentiating NSCs exposed to ELFEFs (1 mT, 50 Hz), the percentage of cells displaying immunoreactivity for neuronal markers (beta-III-tubulin, MAP2) and for Ca(v)1.2 and Ca(v)1.3 channels was markedly increased. NSC-differentiated neurons in ELFEF-exposed cultures also exhibited significant increases in spontaneous firing, in the percentage of cells exhibiting Ca2+ transients in response to KCl stimulation, in the amplitude of these transients and of Ca2+ currents generated by the activation of Ca(v)1 channels. When the Ca(v)1-channel blocker nifedipine (5 microM) was added to the culture medium, the neuronal yield of NSC differentiation dropped significantly, and ELFEF exposure no longer produced significant increases in beta-III-tubulin- and MAP2-immunoreactivity rates. In contrast, the effects of ELFEFs were preserved when NSCs were cultured in the presence of either glutamate receptor antagonists or Ca(v)2.1- and Ca(v)2.2-channel blockers. ELFEF stimulation during the first 24 h of differentiation caused Ca(v)1-dependent increases in the number of cells displaying CREB phosphorylation. Our data suggest that ELFEF exposure promotes neuronal differentiation of NSCs by upregulating Ca(v)1-channel expression and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels, L-Type / metabolism*
  • Cell Differentiation*
  • Cell Proliferation
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Electromagnetic Fields*
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Neurons / cytology*
  • Phenotype
  • Phosphorylation
  • Stem Cells / cytology
  • Time Factors
  • Tubulin / metabolism
  • Up-Regulation*


  • CACNA1C protein, mouse
  • Cacna1d protein, mouse
  • Calcium Channels, L-Type
  • Cyclic AMP Response Element-Binding Protein
  • Microtubule-Associated Proteins
  • Mtap2 protein, mouse
  • Tubulin