Effects of nerve growth factor on whole-cell currents and other electrical membrane properties in cultured dorsal root ganglion neurons from normal and trisomy 16 mice.
The trisomy 16 mouse is considered to be a model of human trisomy 21 (Down syndrome). Dorsal root ganglia (DRG) from trisomy 16 and diploid control fetuses were cultured in the presence of nerve growth factor (NGF) for 10 days, after which NGF was withdrawn from 50% of the dishes. Withdrawing NGF at 10 days did not affect the survival rate of either trisomy 16 or control neurons. With or without NGF, trisomy 16 neurons had a significantly larger inward current (171%, 163%) and larger inward conductance (156%, 166%), a faster rate of depolarization (219%, 149%), and a shorter duration of the action potential (83%, 81%) than control neurons, indicating that these parameters are determined solely by the trisomic state. In the absence of NGF, the outward conductance was significantly larger (143%), and the rate of repolarization was faster (131%), in trisomy cells compared to controls. Withdrawing NGF resulted in a smaller outward conductance (86%) in control neurons and a larger outward conductance (132%) and faster rate of repolarization (118%) in trisomy neurons, indicating that these parameters are NGF-dependent, and that trisomy and control neurons exhibit a differential sensitivity to NGF. This is the first report of a differential sensitivity of trisomic and control neurons to NGF, and demonstrates significant abnormalities in active electrical membrane properties of trisomic DRG neurons.
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892.
E J
EJ
Coan
Z
Z
Galdzicki
S I
SI
Rapoport
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000473:pathology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D012016:Reference Values; D014314:Trisomy
D009414:Nerve Growth Factors