STRETCH, ION CHANNELS, & CARDIAC CELL VOLUME REGULATION

拟议的研究重点是心脏细胞体积调节，以及 将对新鲜分离的兔单个脑室进行研究。 细胞。心肌细胞水肿在缺血的背景下被很好地认识 和充血性心力衰竭。细胞体积调节的缺陷是 与细胞损伤以及收缩和电有关 功能障碍。初步研究表明，牵张激活(SA) 阳离子和阴离子通道可能对心肌细胞体积有贡献 监管。候选人将利用膜片钳和离子选择性 微电极技术表征其性质及其调控 在单通道水平上的SA阳离子和阴离子通道以及它们的 钾对膜电流和细胞内离子活度的贡献， NA和C_1-。这些电生理测量的组合 细胞体积的测定将提供关于基本的 细胞体积调节的机制。此外，假设 细胞骨架元件和环核苷酸对大鼠脑内SA通道的调节 心脏将接受考验。更好地理解细胞的基本机制 音量调节是制定战略的先导，以最大限度减少 缺血和充血性衰竭时的细胞损伤。

The proposed research focuses on cardiac cell volume regulation, and studies will be carried out on freshly isolated single rabbit ventricular cells. Cardiac cell edema is well recognized in the setting of ischemia and congestive heart failure. Defects in cell volume regulation are associated with cellular damage as well as contractile and electrical dysfunction. Preliminary studies suggest that stretch-activated (SA) cation and anion channels may contribute to cardiac cell volume regulation. The candidate will utilize the patch clamp and ion selective microelectrode techniques to characterize the properties and regulation of SA cation and anion channels at the single channel level, and their contribution to membrane currents and intracellular ion activities of K+, Na+, and C1-. The combination of these electrophysiological measurements and cell volume determinations will provide new information about basic mechanisms of cell volume regulation. Further, the hypothesis that cytoskeletal elements and cyclic nucleotides modulate SA channels in heart will be tested. A better understanding of basic mechanisms of cell volume regulation is a precursor to developing strategies to minimize cellular damage during ischemia and congestive failure.