ISSN:
0091-7419
Keywords:
nerve growth factor
;
peripheral neurons
;
ion fluxes
;
transport
;
Life Sciences
;
Molecular Cell Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
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 short-latency events, occurring within minutes of NGF administration. Chick embryo DRG dissociates have proved to be an effective experimental system to investigate short-latency 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 RNA-labeling capability, led to the recognition that NGF controls the transport of selected exogenous substrates, all of which are Na+-coupled 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 pre-equilibrated with extracellular 86Rb+, lose their 86Rb+ 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.
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jss.400130306
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