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.

• Klíčová slova
• Model, bladder, detrusor muscle, interstitial cell, overactive bladder, smooth muscle cell,
• MeSH
• Ca2+-ATPasy metabolismus   MeSH
• endoplazmatické retikulum účinky léků   metabolismus   MeSH
• hyperaktivní močový měchýř patofyziologie   MeSH
• lidé MeSH
• membránové potenciály účinky léků   fyziologie   MeSH
• močový měchýř cytologie   fyziologie   MeSH
• myocyty hladké svaloviny účinky léků   fyziologie   MeSH
• počítačová simulace * MeSH
• ryanodin farmakologie   MeSH
• sarkoplazmatické retikulum účinky léků   metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Ca2+-ATPasy MeSH
• ryanodin MeSH