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 culturing cells for 24 h in the presence of agents known to block astrocytic K+ channels: Cs+, Ba2+, 4-AP and tetraethylammonium (TEA). To determine whether effects were mediated by changes in V-m or pH(i), these parameters were studied electrophysiologically or ratiometrically, using BCECF. Of the four K channel blockers, only Ba2+ depolarized astrocytes significantly. However, all four K+ channel blockers resulted in an alkaline 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 alkaline conditions. These observations suggest that astrocyte proliferation is sensitive to changes in pH(i) and that K+ channel blockers may exhibit their antiproliferative effects through changes in pH(i).