Na+ and K+ dependence of morphological changes of cultured rat cortical astrocytes

Cultured astrocytes display flattened, polygonal morphology in the absence of stimuli, and change into process-bearing stellate cells in response to specific stimuli. In the present study, we investigated possible role of Na+, K+ and Ca2+ in this morphological change of cultured rat cortical astrocytes. Astrocyte stellation induced by dibutyryl cyclic AMP (1 mM), phorbol ester (100 nM) or amyloid beta peptide (20 microM) was partly suppressed by replacing NaCl with choline chloride or LiCl in the extracellular medium or by adding KCl, and was completely abolished by replacing NaCl with KCl. Furthermore, the astrocyte stellation was blocked by the specific Na+-K+ pump inhibitor ouabain. However, it was not significantly affected by removing CaCl2 from the extracellular medium nor by adding the voltage-dependent Ca2+ channel blocker nicardipine. These results suggest that Na+ and K+, but not Ca2+, electrochemical gradients across the plasma membrane are necessary for morphological changes of astrocytes. In addition, amyloid beta25-35-induced stellation was most susceptible to changing Na+ and K+ concentrations or ouabain, while phorbol ester-induced stellation was least sensitive, demonstrating that the Na+ and K+ dependence differs among stimuli.