EXTRACELLULAR POTASSIUM CONCENTRATION REGULATES PROLIFERATION OF IMMATURE CEREBELLAR GRANULE CELLS

The present study examines the effect of depolarizing potassium concen trations on the proliferation of immature rat cerebellar neurons. Cell s inoculated in serum free medium and 5 mM KCl (5 K) showed a high deg ree of H-3-thymidine incorporation that decreased 24-48 h after platin g as differentiation began. During the first 24 h after inoculation, c ells grown in high potassium (25 K), showed a 34 +/- 3% increase (mean +/- S.E.M., n = 12) in H-3-thymidine incorporation as compared with t he values observed in 5 K. After 24 h in vitro, cells grown in 25 K sh owed 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 block ed by MgCl2 and nifedipine, but not by omega-conotoxin GVIA, suggestin g that it is mediated by a Ca2+ influx via voltage-gated calcium chann els (VGCC) of the L-subtype. High potassium-induced cell proliferation was blocked by the mitogen-activated protein kinase kinase (MEK1) inh ibitor (PD98059, 75 mu M). 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 t his increase also was blocked by MgCl2 and nifedipine. These data supp ort the hypothesis that depolarizing activity during neurogenesis play s a role in the modulation of cerebellar granule cells proliferation. (C) 1998 Elsevier Science B.V.