NGF inhibits M/KCNQ currents and selectively alters neuronal excitability in subsets of sympathetic neurons depending on their M/KCNQ current background.
M/KCNQ currents play a critical role in the determination of neuronal excitability. Many neurotransmitters and peptides modulate M/KCNQ current and neuronal excitability through their G protein-coupled receptors. Nerve growth factor (NGF) activates its receptor, a member of receptor tyrosine kinase (RTK) superfamily, and crucially modulates neuronal cell survival, proliferation, and differentiation. In this study, we studied the effect of NGF on the neuronal (rat superior cervical ganglion, SCG) M/KCNQ currents and excitability. As reported before, subpopulation SCG neurons with distinct firing properties could be classified into tonic, phasic-1, and phasic-2 neurons. NGF inhibited M/KCNQ currents by similar proportion in all three classes of SCG neurons but increased the excitability only significantly in tonic SCG neurons. The effect of NGF on excitability correlated with a smaller M-current density in tonic neurons. The present study indicates that NGF is an M/KCNQ channel modulator and the characteristic modulation of the neuronal excitability by NGF may have important physiological implications.
Jia
Zhanfeng
Z
Department of Pharmacology, Hebei Medical University, Shijiazhuang, China 050017.
Bei
Junjie
J
Rodat-Despoix
Lise
L
Liu
Boyi
B
Jia
Qingzhong
Q
Delmas
Patrick
P
Zhang
Hailin
H
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D004553:Electric Conductivity; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D051656:KCNQ Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D051656:KCNQ Potassium Channels; D009419:Nerve Tissue Proteins; D020932:Nerve Growth Factor