Calcium current inactivation during nerve-growth-factor-induced differentiation of PC12 cells

The inactivation of calcium currents during nerve growth factor (NGF)-induced differentiation of rat pheochromocytoma (PC12) cells was investigated. Whole cell calcium and barium currents were recorded in PC12 cells using the patch-clamp method. A shift of the steady-state inactivation curve towards more negative potentials, as well as an increase in the strength of time-dependent inactivation, was observed in differentiating PC12 cells (+NGF) compared to undifferentiated cells (-NGF). The fraction of current inactivated after 200 ms normalized to the peak current amplitude significantly increased from 0.27 +/- 0.01 (n = 39) to 0.39 +/- 0.01 (n = 109) following NGF treatment. The increase in the strength of inactivation preceded the increase in the peak calcium current amplitude observed in PC12 cells during NGF treatment. In differentiating cells, regional differences in the strength of inactivation paralleled differences in current density. Barium currents recorded from growth cones, where the current density was high, showed 30% more inactivation than soma currents. The strength of inactivation of calcium currents in individual cells was not correlated to the effectiveness of nifedipine, nor was the effect of nifedipine on calcium currents altered during differentiation. These results are discussed, suggesting a redistribution of calcium channels during the differentiation of PC12 cells.