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.
- 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
Altered Ca(2+) handling may be responsible for the development of cardiac contractile dysfunctions with advanced age. In the present study, we investigated the roles of oxidative damage to sarcoplasmic reticulum (SR) and expression of Ca(2+)-ATPase (SERCA 2a) and phospholamban in age-associated dysfunction of cardiac SR. SR vesicles were prepared from hearts of 2-, 6-, 15-, and 26-month-old Wistar rats. Although activity of Ca(2+)-ATPase decreased with advancing age, no differences in relative amounts of SERCA 2a and phospholamban protein were observed. On the other hand, significant accumulation of protein oxidative damage occurred with aging. The results of this study suggest that age-related alteration in Ca(2+)-ATPase activity in the rat heart is not a consequence of decreased protein levels of SERCA 2a and phospholamban, but could arise from oxidative modifications of SR proteins. Cellular oxidative damage caused by reactive oxygen species could contribute to age-related alternations in myocardial relaxation.
- MeSH
- Ca2+-ATPasy metabolismus MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- myokard enzymologie patologie MeSH
- oxidace-redukce MeSH
- oxidační stres fyziologie MeSH
- potkani Wistar MeSH
- sarkoplazmatické retikulum enzymologie MeSH
- stárnutí patologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Intracellular free Ca2+ is one of important biological signals regulating a number of cell functions. It has been discussed widely and extensively in several cell types during the past two decades. Attention has been paid to the Ca2+ transportation in mesenchymal stem cells in recent years as mesenchymal stem cells have gained considerable interest due to their potential for cell replacement therapy and tissue engineering. In this paper, roles of intracellular Ca2+ oscillations and its transporters in mesenchymal stem cells have been reviewed.
- MeSH
- Ca2+-ATPasy metabolismus MeSH
- lidé MeSH
- membránové transportní proteiny metabolismus MeSH
- mezenchymální kmenové buňky MeSH
- proteiny přenášející kationty metabolismus MeSH
- pumpa pro výměnu sodíku a vápníku metabolismus MeSH
- vápník metabolismus MeSH
- vápníková signalizace MeSH
- vápníkové kanály metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- Ca2+-ATPasy metabolismus MeSH
- experimentální diabetes mellitus metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- guanidin farmakologie MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- myokard patologie MeSH
- permeabilita buněčné membrány MeSH
- sarkolema metabolismus patologie účinky léků MeSH
- srdce fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
