NIFEDIPINE-INDUCED MORPHOLOGICAL-DIFFERENTIATION OF RAT PHEOCHROMOCYTOMA CELLS

Extension of neuronal processes is fundamental for the establishment o f the intricate network of the nervous system. The rat PC12 pheochromo cytoma cell line is a well-known model system for the study of neurona l differentiation. In the present study the effect of a high-voltage-a ctivated calcium channel blocker, nifedipine, on the cell differentiat ion was investigated. In cells cultured in a modified medium containin g nifedipine (at 2.5 mu M or 5.0 mu M) a decrease of mitotic activity took place on the third day of culturing. An increase of total length and number of processes occurred on the fifth day. A higher concentrat ion of nifedipine (10.0 mu M) considerably suppressed viral functions of the cells. Retraction of processes together with blocking of prolif eration activity was observed. In parallel with these changes, a reduc tion of [Ca2+](i) from 100 +/- 6 nM to 50 +/- 2 nM was detected on the second day of cultivation in 2.5 mu M and 5.0 mu M nifedipine contain ing medium. At 10.0 mu M concentration of nifedipine in the medium a d ecrease in [Ca2+](i) was observed on the first day only (to 76 +/- 8 n M); then the level of free calcium concentration rose dramatically. Th e data obtained allow us to suggest that the decrease of [Ca2+](i) dur ing first two days of PC12 cells culturing in a nifedipine-containing medium could be a factor which stimulated their morphological differen tiation. Published by Elsevier Science Ltd.