Multiple acute effects on the membrane potential of PC12 cells produced by nerve growth factor (NGF)

• Published in: Journal of cellular physiology Vol. 203; no. 3; pp. 501 - 509
• Main Authors: Shimazu, Kazuhiro, Takeda, Kazuyo, Yu, Zu-Xi, Jiang, Hao, Liu, Xu-Wen, Nelson, Phillip G., Guroff, Gordon
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2005
• Subjects: Animals; Calcium Channel Blockers - pharmacology; Cation Transport Proteins - drug effects; Cation Transport Proteins - metabolism; Cations - metabolism; Cell Membrane - drug effects; Cell Membrane - metabolism; Enzyme Inhibitors - pharmacology; Epidermal Growth Factor - pharmacology; Ion Channels - drug effects; Ion Channels - metabolism; Large-Conductance Calcium-Activated Potassium Channels; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mice; Nerve Growth Factor - pharmacology; Neurons - drug effects; Neurons - metabolism; NIH 3T3 Cells; Patch-Clamp Techniques; PC12 Cells; Potassium Channel Blockers - pharmacology; Potassium Channels, Calcium-Activated - antagonists & inhibitors; Potassium Channels, Calcium-Activated - metabolism; Rats; Receptor, Nerve Growth Factor; Receptor, trkA - drug effects; Receptor, trkA - metabolism; Receptors, Nerve Growth Factor - drug effects; Receptors, Nerve Growth Factor - metabolism; Sodium Channels - drug effects; Sodium Channels - metabolism
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.20309

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 p140trk and the low affinity NGF receptor or p75NGF 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 Ca2+‐dependent BK‐type channel blocker, iberiotoxin, and the general Ca2+‐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 La3+ and Gd3+, 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, Ca2+‐dependent potassium currents and non‐selective cation currents. Published 2005 Wiley‐Liss, Inc.