Dopamine-denervation enhances the trophic activity in striatum: Evaluation by morphological and electrophysiological development in PC 12D 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 (I-K) and transient type K+ current (I-A), followed by Ca2+ current (I-Ca) and tetrodotoxin-sensitive Na+ current (I-Na). I-Na was expressed more frequently in L-extract treated cells than N-extract treated cells at D7-9. The larger I-K amplitude in L-extract treatment at D7-9 seemed to be related to the expression of I-Na. Development of I-A was similar at any stage for both treatments. I-Ca development started at D3-5 after treatments, and the amplitude and current density were similar in both treatments. I-Ca was strongly blocked by omega-conotoxin GVIA (3 mu M), 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 I-Na and I-K. (C) 1997 Elsevier Science Ireland Ltd.