TARGET REGULATION OF VOLTAGE-GATED CALCIUM CHANNEL EXPRESSION IN NODOSE GANGLION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 离子通道表达是神经元发育的一个重要方面。在过去的5年里，我们对了解是什么因素调节发育中神经元的离子通道表达很感兴趣。以鸡结状神经节(NG)为模型，我们已经获得了明确的证据，电压门控性钙通道的表达受到靶神经支配和细胞-细胞相互作用的调节。全细胞膜片钳记录显示，未成熟的E7 NG神经元不存在低电压激活(LVA)钙通道。用心脏提取物处理E7 NG神经元48小时，可诱导LVA通道的表达。我们目前的模型表明，NG神经元中LVA钙通道的表达是通过钙依赖机制与心脏衍生因子相互作用来调节的。这项建议旨在研究我们工作模型的一些重要方面，以追求以下具体目标：1)研究心肌组织衍生因子是否介导了己酮对LVA钙通道表达的刺激作用；2)研究六角刺激因子上调LVA钙通道表达的性质；以及3)研究十六烷基己烷对LVA通道表达的刺激作用是否需要通过钙依赖的机制进行蛋白质合成和信号传递。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ion channel expression is an important aspect of neuronal development. Over the last 5 years we have been interested in understanding what factors regulate ion channel expression in developing neurons. Using the chick nodose ganglion (NG) as a model, we have obtained clear evidence that voltage-gated, calcium channel expression is regulated by target innervation and cell-cell interactions. Whole cell patch clamp recordings reveal that low voltage-activated (LVA) calcium channels are not present in immature E7 NG neurons. Treatment of E7 NG neurons with a heart extract for 48 hr induces the expression of LVA channels. Our current model indicates that expression of LVA calcium channels in NG neurons is regulated by interaction with a heart-derived factor via a Ca2+-dependent mechanism. This proposal is designed to investigate some important aspects of our working model by pursuing the following specific aims: 1) To investigate whether a cardiac muscle tissue-derived factor mediates the stimulatory effect of HEx on LVA Ca2+ channel expression; 2) To investigate the nature of the HEx-stimulating factor that upregulates LVA Ca2+ channel expression; and 3) To investigate whether the stimulating effect of HEx on LVA channel expression requires protein synthesis and signaling via a Ca2+-dependent mechanism.