Inward Conductances in Regulation of Colon ic Excitability

胃肠道混合腔内容物并启动腔内容物的向前推进。这 运动活动受兴奋性和抑制性运动神经以及起搏电位的调节 由Cajal间质细胞（ICC）产生。平滑肌细胞作为运动活动的最终效应器。 不管肠道运动神经元和ICC发出的命令如何，如果SM兴奋性机制不起作用， 会导致运动功能障碍。调节静息膜的离子电导 平滑肌细胞中的电位在G1运动的调节中具有中心重要性。离子 肌肉中的机制在设置静息膜电位中起着基本作用， 决定收缩活动。然而，静息膜电位并不仅仅由活性决定， K+通道内向电流，如静息Na+或Ca2+电导，可以移动静息膜 电位值比K+平衡电位更积极。这种“泄漏”电流被认为是由于 多种不同的非选择性阳离子通道（NSCC）的表达。因此， 该应用假设是NSCC，特别是TRP蛋白家族，在 调节结肠中的RMP，并且这些通道的活性可以通过几种不同的第二途径调节。 信使途径或改变结肠肌肉收缩活动的病理状况。我们将 研究以下具体目标。 目标1.基底激活的NSCC的电生理特性是什么？ 目标2.什么是调节基底活化的NSCC的细胞内信号传导机制？ 目标3。基底活化的NSCC的候选分子是什么？ 目标4。在病理生理条件下，基底活化的NSCC的功能作用是什么？ 总之，对这些假说的研究将有助于我们理解基底激活核的功能作用。 NSCC与生理和病理条件下静息膜电位调节的关系。 相关性（参见说明）： 与人类炎症性肠病的相关性

The gastrointestinal tract mixes luminal contents and initiates the forward propulsion of luminal contents. This motor activity is regulated by both excitatory and inhibitory motor nerves as well as by pacemaker potentials generated by interstitial cells of Cajal (ICC). Smooth muscle cells serve as the final effectors of motor activity. Regardless of the commands issued by enteric motor neurons and ICC, if SM excitability mechanisms are not functioning properly motor dysfunction will result. The ionic conductances that regulate resting membrane potential in smooth muscle cells are of central importance in the regulation of Gl motility. The ionic mechanisms in the muscle play a fundamental role in setting the resting membrane potential and thus determining contractile activity. However, resting membrane potential is not determined solely by the activity of K+ channels. Inward currents, such as resting Na+ or Ca2+ conductance can shift the resting membrane potentials to values more positive than the K+ equilibrium potential. This 'leak' current is thought to be due to the expression of a variety of different non-selective cation channels (NSCC). Therefore the working hypothesis for this application is that NSCC, particularly the TRP family of proteins, play an important role in regulating RMP in colon and that the activity of these channels can be regulated by several different second messenger pathways or pathological conditions that alter contractile activity of the colonic muscle. Thus we will investigate the following specific aims. Aim 1. What are the electrophysiological properties of basally activated NSCC? Aim 2. What are the intracellular signaling mechanisms regulating basally activated NSCC? Aim 3. What are the molecular candidates for basally activated NSCC? Aim 4. What are the functional roles of basally activated NSCC in pathophysiological conditions? In summary investigation of these hypotheses will aid our understanding of functional role of basally activated NSCC in relation to regulation of the resting membrane potentials in physiological and pathological conditions. RELEVANCE (See instructions): Relevance to human inflammatory bowel disease