Extracellular potassium concentration regulates proliferation of immature cerebellar granule cells

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 KC1 (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 ω- conotoxin GVIA, suggesting that it is mediated by h 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 μM). 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.