chapter  16
18 Pages

Mechanobiology of Bladder Urothelial Cells

The lower urinary tract, which consists of the bladder, urethra, and urethral sphincters, is responsible for the storage and timely elimination of urine. According to the de™nitions of the International Continence Society, lower urinary tract symptoms (LUTS) can be categorized as storage, voiding, or post-micturition symptoms [1]. LUTS include frequency, urgency, incontinence, intermittency, and the feeling of incomplete emptying, among others. The EpiLUTS study [2] estimated the prevalence of LUTS, occurring at least “often” in individuals aged 40 and older, to be 47.9% for men and 52.5% for women in the United States, the United Kingdom, and Sweden. These symptoms are considered bothersome and affect the quality of life of the patient as well as the patient’s family [3]. The proper functioning of the lower urinary tract is dependent upon complex, coordinated interactions between the structural, muscular, and nervous system components [4]. Unlike most other visceral organs, the bladder and urethra are under both involuntary and voluntary control, providing for both re”exive responses and the conscious control of micturition [5]. Mechanical parameters such as

16.1 Overview ............................................................................................................................... 349 16.2 Urothelial Anatomy and Physiology ..................................................................................... 350

16.2.1 Structure and Function of the Urothelium ................................................................ 350 16.2.2 Neuroanatomy of the Bladder ................................................................................... 351

16.2.2.1 Efferent Pathways ...................................................................................... 351 16.2.2.2 Afferent Pathways ...................................................................................... 351

16.2.3 Physiology of Bladder Filling ................................................................................... 352 16.3 Bladder Mechanosensing Events Mediated by Urothelial Cells........................................... 352

16.3.1 ATP is Released by Urothelial Cells in Response to Mechanical Stimuli ............... 353 16.3.2 Mechanisms of ATP Release .................................................................................... 354 16.3.3 ATP Release via Connexin/Pannexin Hemichannels ............................................... 354 16.3.4 ATP-Sensitive Purinergic Receptors in the Bladder ................................................ 355

16.4 Role of Ion Channels in Urothelial Mechanotransduction ................................................... 356 16.4.1 Mechanosensitive Ion Channels ............................................................................... 356 16.4.2 Electrophysiology of Mechanosensitive Channels ................................................... 356 16.4.3 Mechanosensitive Ion Channels in Bladder Urothelial Cells ................................... 358

16.4.3.1 TRPV1 ....................................................................................................... 358 16.4.3.2 TRPV4 ....................................................................................................... 359 16.4.3.3 Other TRP Channels ..................................................................................360 16.4.3.4 Epithelial Sodium Channels ......................................................................360