Voltage dependent calcium currents in PC12 growth cones and cells during NGF-induced cell growth

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Abstract
The role of calcium currents in the regulation of neurite outgrowth is still rather speculative. As a contribution to this field, macroscopic voltage dependent calcium currents were investigated in relation to the nerve growth factor (NGF)-induced outgrowth of neurites in PC 12 cells. Calcium currents were recorded in isolated growth cones of PC 12 cells using the whole cell patch clamp method. The currents were activated at high voltages and only slightly inactivated with time. The currents were identical to those found in the cell soma of PC 12 cells and similar to the classical high-voltage-activated calcium current found in many neuronal cells. The peak current density in the growth cones was in the same range as in the cell somata. The calcium currents of the cell somata were not modified during the early phase of NGF application, despite the occurrence of NGF-induced soma growth and outgrowth of neurites. The current density at this time was therefore lower in NGF-treated cells than in untreated cells. In a later phase, maximal current amplitudes of NGF-treated cells were higher than in untreated cells indicating an increase in current density to values similar to that found in the untreated cells. In addition, the calcium current inactivation was found to be more pronounced in the NGF-treated cells by that time. The results are discussed with regard to a possible role of calcium currents in the regulation of NGF-induced neurite outgrowth in these cells.