title: Original Research: Combined model of bladder detrusor smooth muscle and interstitial cells.
abstract: Although patients with lower urinary tract symptoms constitute a large and still growing population, understanding of bladder detrusor muscle physiology remains limited. Understanding the interactions between the detrusor smooth muscle cells and other bladder cell types (e.g. interstitial cells, IC) that may significantly contribute to coordinating and modulating detrusor contractions represents a considerable challenge. Computer modeling could help to elucidate some properties that are difficult to address experimentally; therefore, we developed in silico models of detrusor smooth muscle cell and interstitial cells, coupled through gap junctions. The models include all of the major ion conductances and transporters described in smooth muscle cell and interstitial cells in the literature. The model of normal detrusor muscle (smooth muscle cell and interstitial cells coupled through gap junctions) completely reproduced the experimental results obtained with detrusor strips in the presence of several pharmacological interventions (ryanodine, caffeine, nimodipine), whereas the model of smooth muscle cell alone (without interstitial cells) failed to reproduce the experimental results. Next, a model of overactive bladder, a highly prevalent clinical condition in both men and women with increasing incidence at older ages, was produced by modifying several processes as reported previously: a reduction of Ca(2+)-release through ryanodine receptors and a reduction of Ca(2+)-dependent K(+)-conductance with augmented gap junctional coupling. This model was also able to reproduce the pharmacological modulation of overactive bladder. In conclusion, a model of bladder detrusor muscle was developed that reproduced experimental results obtained in both normal and overactive bladder preparations. The results indicate that the non-smooth muscle cells of the detrusor (interstitial cells) contribute significantly to the contractile behavior of bladder detrusor muscle and should not be neglected. The model suggests that reduced Ca(2+)-release through ryanodine receptors and Ca(2+)-dependent K(+)-conductance together with augmented gap junctional coupling might play a major role in overactive bladder pathogenesis.
authors.affiliation: New Technologies Research Center, University of West Bohemia, Pilsen 30614, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: Department of Mechanics, University of West Bohemia, Pilsen 30614, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Byrtus
authors.affiliation: Department of Physiology, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 32300, Czech Republic Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 32300, Czech Republic milan.stengl@lfp.cuni.cz.
authors.forename: Milan
authors.initials: M
authors.lastname: Stengl
mesh_terms: D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003198:Computer Simulation; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology* / Q000502:physiology; D053201:Urinary Bladder, Overactive / Q000503:physiopathology*
chemical_list: D012433:Ryanodine; D000252:Calcium-Transporting ATPases
keywords: Model; bladder; detrusor muscle; interstitial cell; overactive bladder; smooth muscle cell