Abstract
Nerve growth factor (NGF) is likely to exert its trophic action on dorsal root ganglion (DRG) and on sympathetic ganglion neurons by controlling a crucial function of these cells. This function would in turn regulate other cellular machineries and, ultimately, lead to the traditional NGF consequences, such as survival and neuritic growth. A corollary of this view is that the key to NGF action must lie in shortโlatency events, occurring within minutes of NGF administration. Chick embryo DRG dissociates have proved to be an effective experimental system to investigate shortโlatency responses to NGF, in that (1) measurable functional deficits develop over 6 h of NGF deprivation in vitro and (2) delayed presentation of NGF promptly and fully restores the defective function. The first deficit observed in this experimental system, a decline in RNAโlabeling capability, led to the recognition that NGF controls the transport of selected exogenous substrates, all of which are Na^+^โcoupled and depend on an Na^+^ gradient across the neuronal membrane. Subsequent work showed that NGF controlled such transport systems by actually regulating the neuronal ability to control intracellular Na^+^. Under NGF deprivation, the DRG cells accumulate Na^+^ to levels that reflect, and presumably equate, the extracellular Na^+^ concentrations. Conversely, on delayed NGF administration, the accumulated Na^+^ is actively extruded to an extent and at a speed that depends on the NGF concentration. The Na^+^ response is elicited by both Beta and 7S NGF, but not by other proteins tested. All ganglionic systems that display a requirement for exogenous NGF in culture have also displayed the Na^+^ response to NGF. The Na^+^ response is grossly paralleled by a K^+^ response. DRG dissociates, in which intracellular K^+^ has been preโequilibrated with extracellular ^86^Rb^+^, lose their ^86^Rb^+^ over 6 h of NGF deprivation and restore it on delayed NGF administration. The regulation by NGF of mechanisms controlling intracellular Na^+^ and K^+^ levels in their target neurons is likely to occupy an early and fundamentl place in the sequence of events underlying the mode of action of this factor.