Inward Conductances in Regulation of Colon ic Excitability

胃肠道混合管腔内容物并启动管腔内容物的向前推进。这个 运动活动受到兴奋性和抑制性运动神经以及起搏器电位的调节 generated by interstitial cells of Cajal (ICC).平滑肌细胞充当运动活动的最终效应器。 无论肠运动神经元和 ICC 发出的命令如何，如果 SM 兴奋机制不 正常运作会导致运动功能障碍。调节静息膜的离子电导 平滑肌细胞的潜能对于胃肠道运动的调节至关重要。离子型 肌肉中的机制在设置静息膜电位方面发挥着重要作用，因此 determining contractile activity.然而，静息膜电位不仅仅由活性决定 K 通道。内向电流，例如静息 Na 或 Ca2 电导可以改变静息膜 电位值比 K 平衡电位更正。 This 'leak' current is thought to be due to 多种不同的非选择性阳离子通道（NSCC）的表达。因此工作 该应用的假设是 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个不同的第二个调节 改变结肠肌肉收缩活动的信使途径或病理状况。这样我们就会 investigate the following specific aims. 目标 1. 基底细胞激活的 NSCC 的电生理特性是什么？ 目标 2. 调节基底细胞激活的 NSCC 的细胞内信号传导机制是什么？ 目标 3. 基底活化 NSCC 的候选分子有哪些？ 目标 4. 基础激活的 NSCC 在病理生理条件下的功能作用是什么？ 总之，对这些假设的研究将有助于我们理解基底激活的功能作用 NSCC 与生理和病理条件下静息膜电位的调节有关。 相关性（参见说明）： Relevance to human inflammatory bowel disease

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