Title: Dielectric properties of chondrocytes in a changing environment.

描述（由申请人提供）：软骨细胞是产生软骨的唯一细胞类型，占据独特的生物电环境。机械负载通过细胞周围离子和水含量的快速变化产生生物电刺激。软骨细胞对离子梯度变化的反应在调节细胞外基质中起着重要作用 合成.细胞的异常反应可能导致蛋白质的异常沉积，从而导致组织变性和病理后果。通常，对跨细胞膜的离子和渗透梯度的响应是通过离子移动通过通道，因为细胞反应以维持平衡。软骨细胞具有一系列的离子通道，与电兴奋组织相当，但软骨细胞电生理学研究得很不够。离子通道在软骨细胞中的存在现在变得越来越明显，然而，在人类软骨细胞中的广泛研究以及潜在的通道缺陷与疾病的关系尚不充分。该提议将在真实的时间内量化响应于与离子通道基因表达相关的细胞的电化学变化的膜和细胞质的介电性质。我们假设软骨细胞对环境变化的介电反应将依赖于离子通道活性。本提案的目的是（1）使用新型微流体装置记录暴露于渗透压、pH和离子流变化时软骨细胞真实的介电变化。(2)测量软骨细胞中离子通道的基因表达作为对这些变化的响应。(3)软骨细胞在缺氧条件下发挥功能。我们将直接比较正常与缺氧条件下的介电响应，并确定在缺氧条件下软骨细胞中的离子通道活性。据我们所知，我们的结果将是第一个描述软骨细胞介电特性的测量在真实的 时间和与缺氧下的离子通道表达相关，并且将从根本上影响软骨生物学，通过离子通道响应统一软骨中的生物力学和生物电事件。

DESCRIPTION (provided by applicant): Chondrocytes, the only cell type that produces cartilage, occupy a unique bioelectrical environment. Mechanical load generates bioelectrical stimulation through rapid changes in ionic and water content around cells. A chondrocytes response to changing ionic gradients plays an essential role in regulation of extra cellular matrix synthesis. An abnormal response by the cell may result in abnormal deposition of proteins leading to degeneration of tissue with pathological consequences. Typically, response to ionic and osmotic gradients across cell membranes is by ion movement through channels as a cell reacts to maintain equilibrium. Chondrocytes possess an array of ion channels on par with electrically excitable tissues, yet chondrocyte electrophysiology is much understudied. Ion channel presence in chondrocytes is now becoming apparent, however, extensive studies in human chondrocytes and how potential channel defects relate to disease are understudied. This proposal will quantify in real time dielectric properties of the membrane and cytoplasm in response to electrochemical changes to cells related to ion channel gene expression. We hypothesize that dielectric response of chondrocytes to changes in environment will be dependent upon ion channel activity. The objectives of this proposal are (1) to document dielectric changes in chondrocytes in real time when exposed to changes in osmolality, pH and ion flow using a novel microfluidic device. (2) Measure gene expression of ion channels in chondrocytes as a response to these changes. (3) Chondrocytes function under hypoxic conditions. We will directly compare dielectric response under normal versus hypoxic conditions and identify ion channels active in chondrocytes under hypoxic conditions. To our knowledge, our results will be the first description of dielectric properties of chondrocytes measured in real time and correlated to ion channel expression under hypoxia and will fundamentally impact cartilage biology unifying biomechanical and bioelectrical events in cartilage through ion channel response.