Nerve growth factor (NGF)-induced calcium influx and intracellular calcium mobilization in 3T3 cells expressing NGF receptors

The neurotrophins have been implicated in the acute regulation of synaptic plasticity. Neurotrophin-stimulated presynaptic calcium uptake appears to play a key role in this process. To understand the mechanism of neurotrophin-stimulated calcium uptake, the regulation of calcium uptake and intracellular mobilization by nerve growth factor (NGF) was investigated using NCH 3T3 cells stably transfected with either the high affinity NGF receptor p140(trk) (3T3-Trk) or the low affinity NGF receptor p75(NGFR) (3T3-p75). In 3T3-Trk cells, NGF increased both calcium uptake and intracellular calcium mobilization. In 3T3-p75 cells, NGF increased calcium uptake but not intracellular calcium mobilization. K-252a alone increased intracellular calcium in 3T3-Trk cells but not in 3T3-p75 cells. Nifedipine, an inhibitor of calcium uptake through L-type calcium channels, inhibited the action of NGF on both 3T3-Trk cells and 3T3-p75 cells, indicating that both p140(trk) and p75NGFR receptors are linked to nifedipine-sensitive L-type calcium channels. These studies show that either NGF receptor will support increases in intracellular calcium but that p140(trK) does so by increasing both uptake and mobilization, whereas p75NGFR does so by increasing uptake only.