Voltage-sensitive calcium currents are acutely increased by nerve growth factor in PC12 cells

Whole cell calcium currents were recorded from PC12 cells with the perforated patch technique. Currents were evoked by step depolarization from a holding potential of -90 mV. Nerve growth factor (NGF) increased calcium currents through L-type calcium channels by >75% within 3-5 min. This increase was inhibited by K-252a, by nifedipine, and by inhibition or down-regulation of kinase C. Brain-derived neurotrophic factor (BDNF) also increased calcium current, but to a smaller extent. Thus increases in calcium current can be linked to activation of either the high- or the low-affinity nerve growth factor receptor. Increases in presynaptic calcium uptake appear to be a crucial element in the short-term actions of the neurotrophins on neurotransmitter release leading to long-term potentiation. Also, the control of calcium uptake is likely to be an important factor in the long-term actions of the neurotrophins on neuronal survival and neuronal protection. The present data indicate that the PC12 cell may be a useful model for studying the effect of the neurotrophins on calcium uptake.