title: Delayed functional maturation of human neuronal progenitor cells in vitro.
abstract: BACKGROUND
  Differentiation of neuronal progenitor cells (NPCs) in vitro into functional neurons is dependent on a complex cascade of molecular signaling pathways, many of which remain unknown. More specifically, in human NPCs the relationship between the expression of typical neuronal marker proteins and functional properties, such as firing action potential and synaptic transmission, is not well understood. In the present report, the immunocytochemical, morphological and electrophysiological changes that human NPCs undergo during neuronal differentiation in vitro were investigated.
  
  
  METHODS
  Human NPCs were differentiated toward a neuronal phenotype. The time course of the expression of neuronal markers and morphological cell changes was mapped and passive and active electrophysiological membrane properties assessed, throughout the neuronal maturation process.
  
  
  RESULTS
  The acquisition of neuronal markers preceded functional physiological maturation by several weeks. Cell input resistance decreased in the first 2 weeks as cells became less sensitive to input current, while cell capacitance progressively increased with continued neuronal process growth. Functional maturation was observed only by the fifth/sixth week, preceded by a marked increase in Na+ and K+ currents. In contrast, electrophysiological maturation of rodent precursor cells was observed at the end of the first week in vitro. Functionally, human neuronal cells became capable of firing action potentials and forming active synaptic contacts. Many features of the firing pattern however remained immature.
  
  
  CONCLUSIONS
  The results showed that human NPCs develop remarkably slowly and retain immature neuronal features for a prolonged period. The importance of Na-dependent activity for proper neuronal maturation is emphasized.
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Neurocentre, Albert-Ludwig University, Breisacherstrasse 64, 79106 Freiburg im Breisgau, Germany. lepski@gmail.com
authors.forename: G
authors.initials: G
authors.lastname: Lepski
authors.forename: J
authors.initials: J
authors.lastname: Maciaczyk
authors.forename: C E
authors.initials: CE
authors.lastname: Jannes
authors.forename: D
authors.initials: D
authors.lastname: Maciaczyk
authors.forename: J
authors.initials: J
authors.lastname: Bischofberger
authors.forename: G
authors.initials: G
authors.lastname: Nikkhah
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005333:Fetus / Q000033:anatomy & histology; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D012964:Sodium / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012964:Sodium