What do we really know about the external urethral sphincter?

The external urethral sphincter (EUS), composed of skeletal muscle, along with a smooth muscle-lined internal urethral sphincter (IUS), have crucial roles in maintaining continence during bladder filling and facilitating urine flow during voiding. Disruption of this complex activity has profound consequences on normal lower urinary tract function during the micturition cycle. However, relatively little is known about the normal and pathological functions of these particular muscle types, how activity can be manipulated and regulated and why, for example, loss of EUS function and sarcopenia is associated with ageing. Here we discuss the unique physiological, biochemical and metabolic properties of striated and smooth muscle components of the urethral sphincter, which have distinct roles in maintaining continence during bladder filling. Relevant in vivo models for investigation of pathophysiological mechanisms, and for pre-clinical evaluation of therapeutic approaches are reviewed. Electromyography and Urethral Pressure Profile recordings are pivotal to understanding the function and dysfunction of the EUS and for clinical evaluation of e.g. urinary retention. Pre-clinical and clinical studies have revealed that age- or disease-related tissue remodelling that lead to filling/voiding disorders may be mitigated with emerging therapeutic approaches.