Lesser S S, Lo D C
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710.
J Neurosci. 1995 Jan;15(1 Pt 1):253-61. doi: 10.1523/JNEUROSCI.15-01-00253.1995.
Neurotrophic factors have powerful effects on neuronal differentiation and the maintenance of neuronal phenotype, but understanding of their regulation of one important aspect of neuronal function, excitability, remains limited. We have examined the regulation of voltage-gated ion channels by two unrelated neurotrophic factors, NGF and ciliary neurotrophic factor (CNTF), in the SK-N-SH neuroblastoma cell line that is responsive to both factors. NGF and CNTF have strikingly different neuronal specificities and distributions in the nervous system, and might be expected to have significantly different effects on neuronal function. Using whole-cell, perforated-patch, and single-channel recording, we found that treatment with NGF increased levels of voltage-gated sodium, calcium, and potassium currents. In contrast, CNTF treatment increased levels of potassium currents only. NGF and CNTF appeared to regulate the same delayed-rectifier potassium current; in addition, NGF treatment resulted in increased levels of a second potassium current component. Such differential effects of neurotrophic factors on the expression of voltage-gated ion channels would have profound effects on the excitability of target neurons in vivo.
神经营养因子对神经元分化及神经元表型的维持具有强大作用，但对于它们对神经元功能一个重要方面——兴奋性的调控，人们的了解仍然有限。我们研究了两种不相关的神经营养因子，即神经生长因子（NGF）和睫状神经营养因子（CNTF），对SK-N-SH神经母细胞瘤细胞系中电压门控离子通道的调控，该细胞系对这两种因子均有反应。NGF和CNTF在神经系统中具有显著不同的神经元特异性和分布，预计它们对神经元功能会有明显不同的影响。通过全细胞、穿孔膜片钳和单通道记录，我们发现用NGF处理可增加电压门控钠电流、钙电流和钾电流的水平。相反，用CNTF处理仅增加钾电流的水平。NGF和CNTF似乎调控相同的延迟整流钾电流；此外，NGF处理导致第二种钾电流成分的水平增加。神经营养因子对电压门控离子通道表达的这种差异效应，将对体内靶神经元的兴奋性产生深远影响。
