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 Ca2+ channels by measuring radioligand binding. The decrease in Ca2+ channel density, after treatment of the cells with beta-PMA+staurosporine, resulted in a reduced increase in the intracellular Ca2+ 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.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D010456:Peptides, Cyclic / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D051381:Rats; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D020960:omega-Conotoxins
D000470:Alkaloids; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007473:Ion Channels; D009414:Nerve Growth Factors; D010456:Peptides, Cyclic; D047428:Protein Kinase Inhibitors; D020960:omega-Conotoxins; C053423:Conus magus toxin; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium