Control of Na+, K+-pump activity in dorsal root ganglionic neurons by different neuronotrophic agents

Na+, K+-pump activity is indispensable for neuronal survival in vitro and a specific role in its regulation has been demonstrated for the NGF action on its target neurons. We have extended these earlier studies to include two other neuronotrophic agents: the chick eye-derived ciliary neuronotrophic factor (CNTF); and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). CNTF and TPA individually supported the survival of an identical (and maximal) number of embryonic day 10 (E10) dorsal root ganglion (DRG) neurons as did NGF. E10 DRG neurons, seeded as monolayer cultures with 86Rb+ (as K+ tracer) but no trophic supplement in their medium, received NGF, CNTF, TPA, or no agent at 2, 4 or 6 h after seeding. The cultures were analyzed at 6 and 24 h for Na+, K+-pump performance and at 24 h for neuronal survival. Neurons receiving no agent lost their pump activity over the first 6 h and died over the 10-24 h incubation period. Both pump performance and survival were fully supported by any one of the 3 agents when provided at seeding time. Delayed presentation of NGF also led to full restoration of pump activity and survival support, as expected. In contrast, CNTF and TPA failed to correct the increasing pump deficits incurred with increasing times of trophic deprivation, and neuronal survival was proportionally reduced. Delayed addition of CNTF and TPA did, however, prevent further losses of both pump and viability. Close similarities were observed between pump failure and cell losses, demonstrating a linear correlation between pump performance and neuronal survival.(ABSTRACT TRUNCATED AT 250 WORDS)