Abstract
We studied whether nerve growth factor (NGF) can affect the membrane potential and conductance of PC12 cells. We demonstrate that NGF depolarizes the membrane of PC12 cells within a minute and by using transfected NIH 3T3‐Trk and ‐p75 cells we show that both the high affinity NGF receptor p140^trk^ and the low affinity NGF receptor or p75^NGF^ may be involved in the depolarization. Tyrosine kinase inhibitor, K252a, partially inhibited the depolarization, but two agents affecting intracellular calcium movements, Xestospongin C (XeC) and thapsigargin, did not. The early depolarization was eliminated in Na^+^ free solutions and under this condition, a ‘prolonged’ (>2 min) hyperpolarization was observed in PC12 cells in response to NGF. This hyperpolarization was also induced in PC12 cells by epidermal growth factor (EGF). Voltage clamp experiments showed that NGF produced a late (>2 min) increase in membrane conductance. The Ca^2+^‐dependent BK‐type channel blocker, iberiotoxin, and the general Ca^2+^‐dependent K^+^ channel blocker, TEA, attenuated or eliminated the hyperpolarization produced by NGF in sodium free media. Under pretreatment with the non‐selective cation channel blockers La^3+^ and Gd^3+^, NGF hyperpolarized the membrane of PC12 cells. These results suggest that three different currents are implicated in rapid NGF‐induced membrane voltage changes, namely an acutely activated Na^+^ current, Ca^2+^‐dependent potassium currents and non‐selective cation currents. Published 2005 Wiley‐Liss, Inc.