Department of Physiology and Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, 89557, USA.
Arch Biochem Biophys. 2011 Jun 15;510(2):174-81. doi: 10.1016/j.abb.2011.03.009. Epub 2011 Apr 3.
Gastrointestinal (GI) motility ultimately depends upon the contractile activity of the smooth muscle cells of the tunica muscularis. Integrated functioning of multiple tissues and cell types, including enteric neurons and interstitial cells of Cajal (ICC) is necessary to generate coordinated patterns of motor activity that control the movement of material through the digestive tract. The neurogenic mechanisms that govern GI motility patterns are superimposed upon intrinsic myogenic mechanisms regulating smooth muscle cell excitability. Several mechanisms regulate smooth muscle cell responses to neurogenic inputs, including the multifunctional Ca(2+)/calmodulin-stimulated protein kinase II (CaMKII). CaMKII can be activated by Ca(2+) transients from both extracellular and intracellular sources. Prolonging the activities of Ca(2+)-sensitive K(+) channels in the plasma membrane of GI smooth muscle cells is an important regulatory mechanism carried out by CaMKII. Phospholamban (PLN) phosphorylation by CaMKII activates the sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA), increasing both the rate of Ca(2+) clearance from the myoplasm and the frequency of localized Ca(2+) release events from intracellular stores. Overall, CaMKII appears to moderate GI smooth muscle cell excitability. Finally, transcription factor activities may be facilitated by the neutralization of HDAC4 by CaMKII phosphorylation, which may contribute to the phenotypic plasticity of GI smooth muscle cells.
胃肠道（GI）运动最终取决于平滑肌细胞的收缩活动。多个组织和细胞类型的综合功能，包括肠神经元和 Cajal 间质细胞（ICC），对于产生协调的运动活动模式以控制消化道物质的运动是必要的。支配 GI 运动模式的神经机制叠加在调节平滑肌细胞兴奋性的固有肌源性机制上。几种机制调节平滑肌细胞对神经传入的反应，包括多功能 Ca(2+)/钙调蛋白依赖性蛋白激酶 II（CaMKII）。CaMKII 可以被来自细胞外和细胞内源的 Ca(2+)瞬变激活。在胃肠道平滑肌细胞膜中延长 Ca(2+)敏感的 K(+)通道的活性是 CaMKII 执行的一个重要调节机制。CaMKII 磷酸化磷蛋白（PLN）激活肌浆网（SR）Ca(2+)-ATP 酶（SERCA），增加细胞质中 Ca(2+)的清除速率和从细胞内储存库中局部释放 Ca(2+)事件的频率。总体而言，CaMKII 似乎调节胃肠道平滑肌细胞的兴奋性。最后，转录因子的活性可能通过 CaMKII 磷酸化使 HDAC4 中和来促进，这可能有助于胃肠道平滑肌细胞的表型可塑性。
