Drumm Bernard T, Gupta Neha, Mircea Alexandru, Griffin Caoimhin S
Smooth Muscle Research Centre, Department of Life & Health Science, Dundalk Institute of Technology, Dundalk, Ireland.
J Physiol. 2024 Sep 25. doi: 10.1113/JP284744.
Smooth muscle organs of the lower urinary tract comprise the bladder detrusor and urethral wall, which have a reciprocal contractile relationship during urine storage and micturition. As the bladder fills with urine, detrusor smooth muscle cells (DSMCs) remain relaxed to accommodate increases in intravesical pressure while urethral smooth muscle cells (USMCs) sustain tone to occlude the urethral orifice, preventing leakage. While neither organ displays coordinated regular contractions as occurs in small intestine, lymphatics or renal pelvis, they do exhibit patterns of rhythmicity at cellular and tissue levels. In rabbit and guinea-pig urethra, electrical slow waves are recorded from USMCs. This activity is linked to cells expressing vimentin, c-kit and Ca-activated Cl channels, like interstitial cells of Cajal in the gastrointestinal tract. In mouse, USMCs are rhythmically active (firing propagating Ca waves linked to contraction), and this cellular rhythmicity is asynchronous across tissues and summates to form tone. Experiments in mice have failed to demonstrate a voltage-dependent mechanism for regulating this rhythmicity or contractions in vitro, suggesting that urethral tone results from an intrinsic ability of USMCs to 'pace' their own Ca mobilization pathways required for contraction. DSMCs exhibit spontaneous transient contractions, increases in intracellular Ca and action potentials. Consistent across numerous species, including humans, this activity relies on voltage-dependent Ca influx in DSMCs. While interstitial cells are present in the bladder, they do not 'pace' the organ in an excitatory manner. Instead, specialized cells (PDGFRα interstitial cells) may 'negatively pace' DSMCs to prevent bladder overexcitability.
下尿路的平滑肌器官包括膀胱逼尿肌和尿道壁，它们在尿液储存和排尿过程中具有相互的收缩关系。随着膀胱充满尿液，逼尿肌平滑肌细胞（DSMCs）保持松弛以适应膀胱内压的升高，而尿道平滑肌细胞（USMCs）维持张力以阻塞尿道口，防止漏尿。虽然这两个器官都不像小肠、淋巴管或肾盂那样表现出协调的规律性收缩，但它们在细胞和组织水平上确实表现出节律性模式。在兔和豚鼠的尿道中，可记录到USMCs的电慢波。这种活动与表达波形蛋白、c-kit和钙激活氯通道的细胞有关，类似于胃肠道中的 Cajal 间质细胞。在小鼠中，USMCs 有节律地活跃（触发与收缩相关的传播性钙波），并且这种细胞节律在不同组织之间是异步的，并总和形成张力。在小鼠身上进行的实验未能证明在体外调节这种节律性或收缩的电压依赖性机制，这表明尿道张力源于 USMCs 自身“启动”收缩所需的钙动员途径的内在能力。DSMCs 表现出自发性瞬时收缩、细胞内钙增加和动作电位。在包括人类在内的众多物种中，这种活动依赖于 DSMCs 中电压依赖性钙内流。虽然膀胱中存在间质细胞，但它们不会以兴奋性方式“启动”该器官。相反，特殊细胞（PDGFRα 间质细胞）可能会“负向启动”DSMCs 以防止膀胱过度兴奋。
