NGF MODULATION OF SENSORY NEURON ACTION POTENTIALS

这些研究涉及背部兴奋性特性的调节。 根神经节(DRG)神经元受生长因子(GFS)刺激。背根神经节神经元AP是 其特征是在复极化阶段出现了“平台期”，这是由于 内向钙电流。我们已经证明神经生长因子(NGF) 在暴露的2天内缩短AP(APD)的持续时间 背根神经节神经元不再需要NGF来生存。警察局倒退到更长时间 持续时间在抗NGF作用后1天内。这项研究的目的之一是 以确定NGF影响的离子电导变化 警察局。分析将使用3周前分离的胚胎培养物， 新生和成年背根节神经元。首先，通过胞内和全细胞 记录(电流钳位)动作电位的测量，过冲的大小 后超极化阶段(AHP)的幅度和持续时间将为 比较了对照组和NGF处理组的神经元。二、系统分析 调节这些参数的离子电导将被执行 采用全细胞电压钳记录。可能依赖NGF 需要量化的变化将包括那些n个电压依赖的Ca++ (n，L，T)和K+(延迟整流，A电流，K(Ca))导体。 受NGF影响的宏观电流将被识别为特定的通道 拦截者。最早可以检测到时程缩短的时间将是 要下定决心。可能通过综合机制来调节这一效果 将使用RNA和蛋白质合成抑制剂进行测试。其他GFS具有 神经营养活性(碱性成纤维细胞生长因子、表皮生长 因子、胰岛素样生长因子、胰岛素与脑源性神经营养 因素)将测试它们改变DRG兴奋性的能力 属性。此外，化合物本身不是生长因子，但 对DRG神经元具有神经营养活性(8-取代cAMP类似物) 将会受到考验。如果这些分子是活性的，它们的离子基础 效果将与NGF的效果进行比较。两者之间的协同效应 将研究NGF和其他GFS对DRG兴奋性的影响。 这些研究可以确定NGF和其他营养神经的GFs可以 独立于对神经元的影响调节神经元的生理特性 生死存亡。一个长期的目标是理解分子调控 在成熟的神经系统中神经营养因子对通道的影响。今年5月 在某些神经退行性疾病的治疗中有用。

These studies concern regulation of the excitability properties of dorsal root ganglion (DRG) neurons by growth factors (GFs). The DRG neuron AP is characterized by a "plateau" on the repolarizing phase which is due to an inward Ca++ current. We have demonstrated that nerve growth factor (NGF) shortens the duration of the AP (APD) within 2 days for exposure when the DRG neurons no longer require NGF for survival. The APD reverses to longer duration within 1 day after exposure to anti-NGF. One aim of this study is to identify the ionic conductance changes underlying the effect of NGF on the APD. Analysis will use 3-week old dissociated cultures of embryonic, neonatal and adult DRG neurons. First, by intracellular and whole-cell recording (current clamp) measurements of the APD, size of the overshoot and amplitude and duration of the after hyperpolarizing phase (AHP) will be compared in control and NGF-treated neurons. Second, systematic analysis of the ionic conductances mediating these parameters will be carried out using whole-cell voltage clamp recording. Possible NGF-dependent alterations to be quantitated will include those n voltage-dependent Ca++ (N,L,T) and K+ (delayed rectifier, A current, K(ca)) conductances. Macroscopic currents affected by NGF will identified with specific channel blockers. The earliest time at which APD shortening can be detected will be determined. Possible mediation of this effect by synthetic mechanisms will be tested using RNA and protein synthesis inhibitors. Other GFs with neurotrophic activities (basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor, insulin, and brain-derived neurotrophic factor) will be tested for their capacities to alter DRG excitability properties. Also, compounds which are not growth factors per se, but which have neurotrophic activities on DRG neurons (8-substituted cAMP analogs) will be tested. If such molecules are active, the ionic basis of their effects will be compared with those for NGF. Synergistic effects between NGF and other GFs on DRG excitability properties will be investigated. These studies could establish that NGF and other neurotrophic GFs can modulate physiological properties of neurons independently from effects on survival. A long-term objective is to understand the molecular regulation of channels by neurotrophic factors in the mature nervous system. This may be useful in the treatment of certain neurodegenerative diseases.