Inhibition of protein kinases in rat pheochromocytoma (PC12) cells promotes morphological differentiation and down-regulates ion channel expression

We have studied morphological differentiation and ion channel expression in PC12 cells under different culture conditions. Differentiation mediated by nerve growth factor (NGF) was compared with that induced by depletion and inhibition of protein kinases (phorbol ester $\beta $-PMA plus staurosporine). Morphological differentiation was similar under both conditions. However, ion channel densities, studied by means of the patch-clamp technique, were enhanced by NGF and reduced by $\beta $-PMA+staurosporine. Similar changes were also observed for $\omega $-conotoxin-sensitive Ca$^{2+}$ channels by measuring radioligand binding. The decrease in Ca$^{2+}$ channel density, after treatment of the cells with $\beta $-PMA + staurosporine, resulted in a reduced increase in the intracellular Ca$^{2+}$ concentration during K$^{+}$ depolarization. We conclude that morphological differentiation, but not ion channel expression, can occur during depression of protein kinase activities in PC12 cells.