Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
Am J Physiol Renal Physiol. 2020 Aug 1;319(2):F257-F283. doi: 10.1152/ajprenal.00048.2020. Epub 2020 Jul 6.
Urinary bladder smooth muscle (UBSM), also known as detrusor smooth muscle, forms the bladder wall and ultimately determines the two main attributes of the organ: urine storage and voiding. The two functions are facilitated by UBSM relaxation and contraction, respectively, which depend on UBSM excitability shaped by multiple ion channels. In this review, we summarize the current understanding of key ion channels establishing and regulating UBSM excitability and contractility. They include excitation-enhancing voltage-gated Ca (Ca) and transient receptor potential channels, excitation-reducing K channels, and still poorly understood Cl channels. Dynamic interplay among UBSM ion channels determines the overall level of Ca channel activity. The net Ca influx via Ca channels increases global intracellular Ca concentration, which subsequently triggers UBSM contractility. Here, for each ion channel type, we describe UBSM tissue/cell expression (mRNA and protein) profiles and their role in regulating excitability and contractility of UBSM in various animal species, including the mouse, rat, and guinea pig, and, most importantly, humans. The currently available data reveal certain interspecies differences, which complicate the translational value of published animal research results to humans. This review highlights recent developments, findings on genetic knockout models, pharmacological data, reports on UBSM ion channel dysfunction in animal bladder disease models, and the very limited human studies currently available. Among all gaps in present-day knowledge, the unknowns on expression and functional roles for ion channels determined directly in human UBSM tissues and cells under both normal and disease conditions remain key hurdles in the field.
尿路上皮平滑肌（UBSM），又称逼尿肌平滑肌，构成膀胱壁，最终决定了该器官的两个主要特性：储尿和排尿。这两个功能分别通过 UBSM 的松弛和收缩来实现，这取决于由多种离子通道塑造的 UBSM 兴奋性。在这篇综述中，我们总结了目前对建立和调节 UBSM 兴奋性和收缩性的关键离子通道的理解。它们包括增强兴奋性的电压门控 Ca（Ca）和瞬时受体电位通道、降低兴奋性的 K 通道，以及仍未完全了解的 Cl 通道。UBSM 离子通道之间的动态相互作用决定了整体 Ca 通道活性水平。通过 Ca 通道的净 Ca 内流增加了细胞内 Ca 浓度，从而引发 UBSM 收缩性。在这里，我们描述了每种离子通道类型在各种动物物种（包括小鼠、大鼠和豚鼠，以及最重要的人类）中的 UBSM 组织/细胞表达（mRNA 和蛋白）谱及其在调节 UBSM 兴奋性和收缩性中的作用。目前可用的数据揭示了某些种间差异，这使得已发表的动物研究结果在人类中的转化价值变得复杂。本综述强调了最近的发展、基因敲除模型的发现、药理学数据、动物膀胱疾病模型中 UBSM 离子通道功能障碍的报告，以及目前可用的非常有限的人类研究。在目前知识的所有空白中，直接在正常和疾病条件下的人类 UBSM 组织和细胞中确定的离子通道的表达和功能作用的未知仍然是该领域的关键障碍。
