title: Extracellular potassium concentration regulates proliferation of immature cerebellar granule cells.
abstract: The present study examines the effect of depolarizing potassium concentrations on the proliferation of immature rat cerebellar neurons. Cells inoculated in serum free medium and 5 mM KCl (5 K) showed a high degree of 3H-thymidine incorporation that decreased 24-48 h after plating as differentiation began. During the first 24 h after inoculation, cells grown in high potassium (25 K), showed a 34 +/- 3% increase (mean +/- S.E.M., n = 12) in 3H-thymidine incorporation as compared with the values observed in 5 K. After 24 h in vitro, cells grown in 25 K showed 23 +/- 3% (mean +/- S.E.M., n = 3) less DNA synthesis than those inoculated in 5 K. The increase in DNA synthesis due to 25 K was blocked by MgCl2 and nifedipine, but not by omega-conotoxin GVIA, suggesting that it is mediated by a Ca2+ influx via voltage-gated calcium channels (VGCC) of the L-subtype. High potassium-induced cell proliferation was blocked by the mitogen-activated protein kinase kinase (MEK1) inhibitor (PD98059, 75 microM). The number of neurons counted after 48 h in vitro in 25 K was 35-100% above of the number obtained with 5 K and this increase also was blocked by MgCl2 and nifedipine. These data support the hypothesis that depolarizing activity during neurogenesis plays a role in the modulation of cerebellar granule cells proliferation.
authors.affiliation: Centro de Investigaciones Médicas Albert Einstein (CIMAE), Buenos Aires, Argentina.
authors.forename: L N
authors.initials: LN
authors.lastname: Borodinsky
authors.forename: M L
authors.initials: ML
authors.lastname: Fiszman
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D048369:MAP Kinase Kinase 1; D015636:Magnesium Chloride / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases; D009474:Neurons / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D005419:Flavonoids; D010455:Peptides; D015636:Magnesium Chloride; D011189:Potassium Chloride; D020866:omega-Conotoxin GVIA; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D009543:Nifedipine; D011188:Potassium; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D013936:Thymidine