Multiple acute effects on the membrane potential of PC12 cells produced by nerve growth factor (NGF).
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 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.
Shimazu
Kazuhiro
K
Section on Growth Factors, NICHD, National Institutes of Health (NIH), Maryland, USA.
Takeda
Kazuyo
K
Yu
Zu-Xi
ZX
Jiang
Hao
H
Liu
Xu-Wen
XW
Nelson
Phillip G
PG
Guroff
Gordon
G
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000187:drug effects / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000187:drug effects / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D002121:Calcium Channel Blockers; D027682:Cation Transport Proteins; D002412:Cations; D004791:Enzyme Inhibitors; D007473:Ion Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D015222:Sodium Channels; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA