ASTROCYTE proliferation was studied in primary cultures of rat spinal
cord by [H-3]thymidine uptake and was significantly reduced by culturi
ng cells for 24 h in the presence of agents known to block astrocytic
K+ channels: Cs+, Ba2+, 4-AP and tetraethylammonium (TEA). To determin
e whether effects were mediated by changes in V-m or pH(i), these para
meters were studied electrophysiologically or ratiometrically, using B
CECF. Of the four K channel blockers, only Ba2+ depolarized astrocytes
significantly. However, all four K+ channel blockers resulted in an a
lkaline shift in pH(i). Under culture conditions that altered pH(i) in
a defined way, proliferation strongly depended on pH(i), with highest
rates at pH similar to 6.7 and growth inhibition at more acidic or al
kaline conditions. These observations suggest that astrocyte prolifera
tion is sensitive to changes in pH(i) and that K+ channel blockers may
exhibit their antiproliferative effects through changes in pH(i).