Regulation of voltage- and ligand-gated currents in rat hippocampal progenitor cells in vitro.
Growth medium and substrate regulate the proliferation and differentiation of neural progenitor cells in vitro and the expression of cell type-specific histochemical markers. An important question is whether neural progenitor cells exhibit voltage- and ligand-gated currents, features characteristic of neurons, and whether these currents are regulated differentially by growth conditions. Another issue of interest is whether passaged progenitor cells, after expansion with basic fibroblast growth factor (FGF-2), exhibit the same degree of plasticity as their primary counterparts, or whether they are more committed to a particular phenotype. In primary cultures of embryonic rat hippocampal progenitor cells, growth in proliferative conditions (FGF-2) was associated with low levels of sodium, calcium, N-methyl-D-aspartate (NMDA), and kainate currents compared with other growth conditions. After multiple passages in the continued presence of FGF-2, sodium, calcium, and NMDA, responses declined further; interestingly, kainate and gamma-aminobutyric acid (GABA) responses remained substantial. Moreover, the expression of functional channels and receptors in primary cultures of progenitor cells is up-regulated strongly by growth factors such as BDNF, and NT-3, whereas sodium and calcium currents in passaged cultures respond to such growth conditions to a lesser extent. Kainate and GABA responses were present to a significant extent in passaged cultures, independent of growth condition. We conclude that environmental cues regulate different channels and receptors in distinct ways in neural progenitor cells.
Sah
D W
DW
Signal Pharmaceuticals Incorporated, San Diego, California 92121, USA. dsah@SignalPharm.-com
Ray
J
J
Gage
F H
FH
D000818:Animals; D000918:Antibody Specificity; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D015640:Ion Channel Gating / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008024:Ligands; D016202:N-Methylaspartate / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D020933:Neurotrophin 3; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013234:Stem Cells / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D016875:tau Proteins / Q000032:analysis / Q000276:immunology
D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D018690:Excitatory Amino Acid Agonists; D008024:Ligands; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D016875:tau Proteins; D005680:gamma-Aminobutyric Acid; D005346:Fibroblast Growth Factors; D016202:N-Methylaspartate; D012964:Sodium; D007608:Kainic Acid