Dopamine-denervation enhances the trophic activity in striatum: evaluation by morphological and electrophysiological development in PC12D cells.
To evaluate the possibility that dopamine (DA) denervation enhances the trophic activity in striatum, normal or DA-depleted striatal tissue extract (N- or L-extract, respectively) was obtained, and their trophic effects on PC12D cells were investigated from the viewpoints of differentiation using morphological and electrophysiological analyses. Treatment with N- or L-extract induced neurite outgrowth in a concentration-dependent manner, and induced the enlargement of cell size. These effects were stronger in L-extract than in N-extract. Cation currents were investigated in whole cell patch-clamp mode. Development of cation current started with delayed-rectifier type K+ current (IK) and transient type K+ current (IA), followed by Ca2+ current (ICa) and tetrodotoxin-sensitive Na+ current (INa). INa was expressed more frequently in L-extract treated cells than N-extract treated cells at D7-9. The larger IK amplitude in L-extract treatment at D7-9 seemed to be related to the expression of INa. Development of IA was similar at any stage for both treatments. ICa development started at D3-5 after treatments, and the amplitude and current density were similar in both treatments. ICa was strongly blocked by omega-conotoxin GVIA (3 microM), indicating that N-type channels were mainly expressed after treatments. The data suggests that L-extract has stronger effects to hasten the differentiation of PC12D cells than N-extract by promoting the neurite outgrowth, cell enlargement and expression of voltage-dependent cation channels, especially INa and IK.
Hida
H
H
Department of Physiology, Nagoya City University Medical School, Japan.
Fukuda
A
A
Fujimoto
I
I
Shimano
Y
Y
Nakajima
K
K
Hashitani
T
T
Nishino
H
H
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D003714:Denervation; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D017072:Neostriatum / Q000502:physiology* / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects; D014020:Tissue Extracts / Q000494:pharmacology
D015220:Calcium Channels; D009414:Nerve Growth Factors; D015221:Potassium Channels; D015222:Sodium Channels; D014020:Tissue Extracts; D016222:Fibroblast Growth Factor 2; D004298:Dopamine