Sanders Kenton M, Baker Salah A, Drumm Bernard T, Kurahashi Masaaki
Department of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, NV, USA.
Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Iowa, Iowa, Iowa City, USA.
Adv Exp Med Biol. 2022;1383:229-241. doi: 10.1007/978-3-031-05843-1_22.
Years ago gastrointestinal motility was thought to be due to interactions between enteric nerves and smooth muscle cells (SMCs) in the tunica muscularis. Thus, regulatory mechanisms controlling motility were either myogenic or neurogenic. Now we know that populations of interstitial cells, c-Kit (interstitial cells of Cajal or ICC), and PDGFRα cells (formerly "fibroblast-like" cells) are electrically coupled to SMCs, forming the SIP syncytium. Pacemaker and neurotransduction functions are provided by interstitial cells through Ca release from the endoplasmic reticulum (ER) and activation of Ca-activated ion channels in the plasma membrane (PM). ICC express Ca-activated Cl channels encoded by Ano1. When activated, Ano1 channels produce inward current and, therefore, depolarizing or excitatory effects in the SIP syncytium. PDGFRα cells express Ca-activated K channels encoded by Kcnn3. These channels generate outward current when activated and hyperpolarizing or membrane-stabilizing effects in the SIP syncytium. Inputs from enteric and sympathetic neurons regulate Ca transients in ICC and PDGFRα cells, and currents activated in these cells conduct to SMCs and regulate contractile behaviors. ICC also serve as pacemakers, generating slow waves that are the electrophysiological basis for gastric peristalsis and intestinal segmentation. Pacemaker types of ICC express voltage-dependent Ca conductances that organize Ca transients, and therefore Ano1 channel openings, into clusters that define the amplitude and duration of slow waves. Ca handling mechanisms are at the heart of interstitial cell function, yet little is known about what happens to Ca dynamics in these cells in GI motility disorders.
多年前，胃肠蠕动被认为是由于肌层中肠神经与平滑肌细胞（SMC）之间的相互作用所致。因此，控制蠕动的调节机制要么是肌源性的，要么是神经源性的。现在我们知道，间质细胞群体、c-Kit（Cajal间质细胞或ICC）和PDGFRα细胞（以前称为“成纤维细胞样”细胞）与SMC电耦合，形成SIP合胞体。间质细胞通过从内质网（ER）释放Ca以及激活质膜（PM）中的Ca激活离子通道来提供起搏器和神经传导功能。ICC表达由Ano1编码的Ca激活Cl通道。激活后，Ano1通道产生内向电流，因此在SIP合胞体中产生去极化或兴奋作用。PDGFRα细胞表达由Kcnn3编码的Ca激活K通道。这些通道激活时产生外向电流，并在SIP合胞体中产生超极化或膜稳定作用。来自肠神经和交感神经神经元的输入调节ICC和PDGFRα细胞中的Ca瞬变，这些细胞中激活的电流传导至SMC并调节收缩行为。ICC还充当起搏器，产生慢波，慢波是胃蠕动和肠节段性运动的电生理基础。起搏器类型的ICC表达电压依赖性Ca电导，该电导将Ca瞬变以及因此的Ano1通道开放组织成簇，从而定义慢波的幅度和持续时间。Ca处理机制是间质细胞功能的核心，但对于胃肠动力障碍中这些细胞的Ca动态变化知之甚少。
