REDUCTION OF GLIAL PROLIFERATION BY K+ CHANNEL BLOCKERS IS MEDIATED BY CHANGES IN PH(I)

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).