项目名称: 感觉神经元Ca2+激活氯电流的分子基础及Ca2+特异性选择机制
项目编号: No.31270882
项目类型: 面上项目
立项/批准年度: 2013
项目学科: 生物科学
项目作者: 张海林
作者单位: 河北医科大学
项目金额: 80万元
中文摘要: 钙激活氯离子通道(Ca2+-activated Chloride Channels, CaCCs)在感觉传导、上皮细胞分泌以及平滑肌细胞收缩等过程中发挥着重要的作用。最近的一系列研究提示CaCC在感觉神经元功能中发挥重要作用。根据我们自己及他人的前期工作我们提出如下假设,背跟神经节(DRG)特定的神经元亚型中可能有不同的CaCC功能表达,即小直径痛感觉神经元中为TMEM16A,中、大直径机械、位置感觉神经元为Bestrophin-1。 本研究将通过如下研究内容验证我们的假设:DRG特定的神经元亚型中是否存在不同类型的CaCC;这些不同类型CaCC的分子基础是什么;TMEM16A和Bestrophin-1是否分别构成膜受体(内Ca2+释放)和膜电压依赖性钙通道(外Ca2+内流)激活的CaCC;导致TMEM16A和Bestrophin-1选择性地被不同途径来源的Ca2+激活的特异性机制是什么
中文关键词: 钙离子;氯离子通道;感觉神经元;分子基础;调节
英文摘要: Ca2+-activated Cl- current (CaCC) is an important biological current which is crucial for the epithelial secretion, smooth muscle contraction and sensory processing. Recent studies indicate important role for CaCC in sensory functions. Based on our own and others studies, we propose the following hypothesis: different functional CaCC may exist in subpopulation DRG neurons, with TMEM16A to be the CaCC in small nociceptor DRG neurons and Bestrophin-1 to be the CaCC in medium and large mechano-sensitive and proprioceptive neurons. This application is designed to provide the support for the hypothesis through the following studies: to study whether there exist CaCC with different properties in subpopulation of DRG neurons, the molecular basis of these different CaCC; to study whether TMEM16A and Bestrophin-1 underlie the membrane receptor (intracellular Ca2+ release) activated CaCC and Ca2+ channels ( Ca2+ influx) activated CaCC, respectively; and to study the mechanism for activation of TMEM16A and Bestrophin-1 by different source of Ca2+.
英文关键词: Ca2+;Cl ion channel;sensory neuron;molecular basis;regulation