γEpithelial Na+ Channel (γENaC) and the Acid-Sensing Ion Channel 1 (ASIC1) expression in the urothelium of patients with neurogenic detrusor overactivity

Objective To investigate the expression of two types of cation channels, gamma Epithelial Na+ Channel (gamma ENaC) and the Acid-Sensing Ion Channel 1 (ASIC1), in the urothelium of controls and in patients affected by neurogenic detrusor overactivity (NDO). In parallel, urodynamic parameters were collected and correlated to the immunohistochemical results. Patients Subjects and Methods Four controls and 12 patients with a clinical diagnosis of NDO and suprasacral spinal cord lesion underwent urodynamic measurements and cystoscopy. Cold-cup biopsies were frozen and processed for immunohistochemistry and Western Blot. Spearman's correlation coefficient between morphological and urodynamic data was applied. One-way ANOVA followed by Newman-Keuls multiple comparison post hoc test was applied for Western Blot results. Results In the controls, gamma ENaC and ASIC1 were expressed in the urothelium with differences in their cell distribution and intensity. In patients with NDO, both markers showed consistent changes either in cell distribution and labelling intensity compared with the controls. A significant correlation between a higher intensity of gamma ENaC expression in the urothelium of patients with NDO and lower values of bladder compliance was detected. Conclusions The present findings show important changes in the expression of gamma ENaC and ASIC1 in NDO human urothelium. Notably, while the changes in gamma ENaC might impair the mechanosensory function of the urothelium, the increase of ASIC1 might represent an attempt to compensate for the excess in local sensitivity.