Ion channels in the human urinary rhabdosphincter: Identification of pharmacological targets regulating the muscle tone

The rhabdosphincter (RS) plays a pivotal role in urinary continence. In patients suffering from urinary stress incontinence after radical prostatectomy the function of the RS, not the smooth musculature of the urethra, is impaired. Degeneration or scars that occur after prostate surgery lead to morphological as well as functional defects of the rhabdosphincter. Subsequently, these changes represent the pathophysiologic basis for an impairment of the urethral closure mechanism. Furthermore, the increasing incidence in urinary stress-incontinence with advancing age is directly correlated to spontaneous apoptosis of the muscle cells of the RS. This process may lead to an age-dependent reduction in the number of striated muscle cells and represent a possible cause of urinary incontinence. First steps towards a new therapy of sphincter insufficiency were recently reported by Chancellor and Yokoyama. Using a rat model, these authors demonstrated that injections of autologous myoblasts that have been taken from skeletal muscle biopsies into the urethra are feasible. In order to investigate the potential of this new therapy, it was necessary to analyse the cellular properties of myoblasts taken from the RS and skeletal muscle (SKM) in more detail. When the project was started it was not known if the myoblasts generated from other sources (i.e. a biopsy of a limb SKM) are fully compatible to RS myoblasts. Muscle biopsies were collected from the prostatic part of the RS, the RS of male pigs and the porcine lower limb skeletal muscle. Ion channels were studied by means of the patch-clamp technique. Only one subtype each of voltage gated Na+ and Ca2+ channels was observed in porcine RS and porcine lower limb of skeletal muscle (LLSKM). Two types of voltage gated Ca2+ channels were identified in human RS cells. The porcine RS and LLSKM myoblasts displayed similar fusion competence. CONCLUSIONS: Porcine RS and LLSKM myoblasts and human RS and human skeletal muscle cells show a high degree of similarity. Injection of autologous skeletal muscle myoboblasts in the lower urinary tract might, therefore, represent a promising approach to treat stress incontinence after radical prostatectomy.