Cameron J S, Dryer L, Dryer S E
Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5513, USA.
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2832-6. doi: 10.1073/pnas.041394098. Epub 2001 Feb 6.
The development of functional Ca(2+)-activated K(+) channels (K(Ca)) in chick ciliary ganglion (CG) neurons requires interactions with afferent preganglionic nerve terminals. Here we show that the essential preganglionic differentiation factor is an isoform of beta-neuregulin-1. beta-Neuregulin-1 transcripts are expressed in the midbrain preganglionic Edinger-Westphal nucleus at developmental stages that coincide with or precede the normal onset of macroscopic K(Ca) in CG neurons. Injection of beta-neuregulin-1 peptide into the brains of developing embryos evoked a robust stimulation of functional K(Ca) channels at stages before the normal appearance of these channels in CG neurons developing in vivo. Conversely, injection of a neutralizing antiserum specific for beta-neuregulin-1 inhibited the development of K(Ca) channels in CG neurons. Low concentrations of beta-neuregulin-1 evoked a robust increase in whole-cell K(Ca) in CG neurons cocultured with iris target tissues. By contrast, culturing CG neurons with iris cells or low concentrations of beta-neuregulin-1 by themselves was insufficient to stimulate K(Ca). These data suggest that the preganglionic factor required for the development of K(Ca) in ciliary ganglion neurons is an isoform of beta-neuregulin-1, and that this factor acts in concert with target-derived trophic molecules to regulate the differentiation of excitability.
鸡睫状神经节（CG）神经元中功能性钙激活钾通道（K（Ca））的发育需要与传入的节前神经末梢相互作用。我们在此表明，关键的节前分化因子是β-神经调节蛋白-1的一种亚型。β-神经调节蛋白-1转录本在中脑节前动眼神经核中表达，其发育阶段与CG神经元中宏观K（Ca）正常出现的时间一致或早于该时间。向发育中的胚胎脑内注射β-神经调节蛋白-1肽，在体内发育的CG神经元中这些通道正常出现之前的阶段，可强烈刺激功能性K（Ca）通道。相反，注射针对β-神经调节蛋白-1的中和抗血清可抑制CG神经元中K（Ca）通道的发育。低浓度的β-神经调节蛋白-1可使与虹膜靶组织共培养的CG神经元的全细胞K（Ca）显著增加。相比之下，单独将CG神经元与虹膜细胞或低浓度的β-神经调节蛋白-1一起培养不足以刺激K（Ca）。这些数据表明，睫状神经节神经元中K（Ca）发育所需的节前因子是β-神经调节蛋白-1的一种亚型，并且该因子与靶源性营养分子协同作用以调节兴奋性的分化。
