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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。离子通道表达是神经元发育的重要方面。在过去的5年里，我们一直有兴趣了解哪些因素调节发育中的神经元离子通道的表达。以鸡的结状神经节为模型，我们获得了明确的证据，电压门控性钙通道的表达受靶神经支配和细胞-细胞相互作用的调节。全细胞膜片钳记录显示，低电压激活（LVA）的钙通道不存在于未成熟的E7 NG神经元。用心脏提取物处理E7 NG神经元48小时诱导LVA通道的表达。我们目前的模型表明，NG神经元中LVA钙通道的表达通过与心脏衍生因子的相互作用经由Ca 2+依赖性机制来调节。本研究的主要目的是：1）研究心肌组织源性因子是否介导HEx对LVA Ca ~（2+）通道表达的刺激作用; 2）研究HEx刺激LVA Ca ~（2+）通道表达的机制; 3）研究HEx对LVA通道表达的刺激作用是否需要通过Ca 2+依赖性机制的蛋白质合成和信号传导。

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.