Reseaarch on the function and development of new therapy for Ion channels in the lower urinary tract

在储尿阶段，机械牵拉刺激膀胱传入。这些膀胱传入感觉神经由小直径的Aδ-和C-纤维组成，在腹下神经和盆神经中行进。神经解剖学研究揭示了膀胱壁内复杂的神经网络。强调膀胱传入末梢中的机械感觉转导的确切机制仍然不明确;然而，广泛的离子通道（例如，TTX抗性Na+通道、Kv通道和超极化激活的环核苷酸门控阳离子通道、变性蛋白/上皮Na+通道）和受体（例如，TRPV 1、TRPM 8、TRPA 1、P2 X 2/3等）在膀胱传入末梢中被激活。已经在膀胱传入末梢处鉴定出，并且涉及传入信号的产生和调节，所述传入信号由广泛的膀胱刺激引起，包括生理性膀胱充盈、有害膨胀、寒冷、化学刺激和炎症。哺乳动物瞬时受体电位（TRP）家族由28个通道组成，可细分为6个不同的类别：TRPV（香草素）、TRPC（典型）、TRPM（Melastatin）、TRPP（多囊蛋白）、TRPML（粘磷脂）和TRPA（锚蛋白）。TRP通道通过多种物理（电压、热、冷、机械应力）或化学（pH、渗透压）刺激以及通过结合特异性配体来激活，使其能够在细胞水平上充当多功能传感器。TRPV 1、TRPV 2、TRPV 4、TRPM 8和TRPA 1已在泌尿生殖道的不同部位进行了描述。虽然目前只有TRPV 1在TRP中得到了广泛的研究，但关于其他TRP通道、离子通道和受体在泌尿生殖道病理生理学中的作用的证据正在慢慢积累，并可能为膀胱功能障碍的治疗提供新的策略。

In the urine storage phase, mechanical stretch stimulates bladder afferents. These urinary bladder afferent sensory nerves consist of small diameter Aδ- and C-fibers running in the hypogastic and pelvic nerves. Neuroanatomical studies have revealed a complex neuronal network within the bladder wall. The exact mechanisms that underline mechano-sensory transduction in bladder afferent terminals remain ambiguous ; however, a wide range of ion channels (e.g. TTX-resistant Na+ channels, Kv channels and hyperpolarization-activated cyclic nucleotidegated cation channels, degenerin/epithelial Na+ channel), and receptors (e.g. TRPV1, TRPM8, TRPA1, P2X2/3, etc.) have been identified at bladder afferent terminals and have implicated in the generation and modulation of afferent signals, which are elcited by a wide range of bladder stimulations including physiological bladder filling, noxious distension, cold, chemical irritation and inflammation. The mammalian transient receptor potential (TRP) family consists of 28 channels that can be subdivided into six different classes : TRPV (vanilloid), TRPC (canonical), TRPM (Melastatin), TRPP (Polycystin), TRPML (Mucolipin), and TRPA (Ankyrin). TRP channels are activated by a diversity of physical (voltage, heat, cold, mechanical stress) or chemical (pH, osmolality) stimuli and by binding of specific ligands, enabling them to act as multifunctional sensors at the cellular level. TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 have been described in different parts of the urogenital tract. Although only TRPV1 among TRPs has been extensively studied so far, more evidence is slowly accumulating about the role of other TRP channels, ion channels, and receptors in the pathophysiology of the urogenital tract, and may provide a new strategy for the treatment of bladder dysfunction.