Potassium chloride inhibits proliferation of cerebellar granule neuron progenitors.
CNS neurogenesis involves a critical transition where neuronal progenitors exit the cell cycle and initiate terminal differentiation. Recent experiments have suggested that depolarization inhibits DNA synthesis in cortical progenitors. Depolarization of proliferating neuronal progenitors may thus activate mechanisms that prevent proliferation and allow the initiation of terminal differentiation. We present evidence that depolarizing concentrations of KCl (25-50 mM) reduce proliferation of developing postnatal cerebellar granule cells in culture. These studies show that KCl antagonizes the mitogenic response of granule cells to insulin-like growth factor-I (IGF-I) and that this reduction in proliferating cells is not the result of a selective cell death. We also examined the differentiation of granule cell cultures using Brn-5 expression as an early differentiation marker. In vivo Brn-5 expression occurs soon after developing granule cells exit the cell cycle and begin their final differentiation. In control cultures and cultures treated with high concentrations of KCl Brn-5 expression increased over 24-48 h of culture. Our results suggest depolarizing concentrations of KCl antagonize proliferation of cerebellar granule neuron progenitors however allow their continued differentiation.
Cui
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Department of Pharmacology, University of Maryland School of Medicine, Baltimore 21201, USA.
Bulleit
R F
RF
D000818:Animals; D001973:Bromodeoxyuridine / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000276:immunology; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D050809:POU Domain Factors; D011189:Potassium Chloride / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D014157:Transcription Factors / Q000276:immunology
D004268:DNA-Binding Proteins; D008934:Mitogens; D050809:POU Domain Factors; C489996:Pou6f1 protein, mouse; D014157:Transcription Factors; D011189:Potassium Chloride; D007334:Insulin-Like Growth Factor I; D001973:Bromodeoxyuridine