| Online-Ressource |
Verfasst von: | Sproßmann, Franz [VerfasserIn]  |
| Pankert, Patrick [VerfasserIn]  |
| Sausbier, Ulrike [VerfasserIn]  |
| Wirth, Angela [VerfasserIn]  |
| Zhou, Xiao-Bo [VerfasserIn]  |
| Madlung, Johannes [VerfasserIn]  |
| Zhao, Hong [VerfasserIn]  |
| Bucurenciu, Iancu [VerfasserIn]  |
| Jakob, Andreas [VerfasserIn]  |
| Lamkemeyer, Tobias [VerfasserIn]  |
| Neuhuber, Winfried [VerfasserIn]  |
| Offermanns, Stefan [VerfasserIn]  |
| Shipston, Michael J. [VerfasserIn]  |
| Korth, Michael [VerfasserIn]  |
| Nordheim, Alfred [VerfasserIn]  |
| Ruth, Peter [VerfasserIn]  |
| Sausbier, Matthias [VerfasserIn]  |
Titel: | Inducible knockout mutagenesis reveals compensatorymechanisms elicited by constitutive BK channeldeficiency in overactive murine bladder |
Verf.angabe: | Franz Sprossmann, Patrick Pankert, Ulrike Sausbier, Angela Wirth, Xiao-Bo Zhou, Johannes Madlung, Hong Zhao, Iancu Bucurenciu, Andreas Jakob, Tobias Lamkemeyer, Winfried Neuhuber, Stefan Offermanns, Michael J. Shipston, Michael Korth, Alfred Nordheim, Peter Ruth and Matthias Sausbier |
E-Jahr: | 2009 |
Jahr: | 25 February 2009 |
Umfang: | 18 S. |
Fussnoten: | Gesehen am 11.11.2019 |
Titel Quelle: | Enthalten in: Vereinigung der Europäischen Biochemischen GesellschaftenThe FEBS journal |
Ort Quelle: | Oxford [u.a.] : Wiley-Blackwell, 2005 |
Jahr Quelle: | 2009 |
Band/Heft Quelle: | 276(2009), 6, Seite 1680-1697 |
ISSN Quelle: | 1742-4658 |
Abstract: | The large-conductance, voltage-dependent and Ca2+-dependent K+ (BK) channel links membrane depolarization and local increases in cytosolic free Ca2+ to hyperpolarizing K+ outward currents, thereby controlling smooth muscle contractility. Constitutive deletion of the BK channel in mice (BK−/−) leads to an overactive bladder associated with increased intravesical pressure and frequent micturition, which has been revealed to be a result of detrusor muscle hyperexcitability. Interestingly, time-dependent and smooth muscle-specific deletion of the BK channel (SM-BK−/−) caused a more severe phenotype than displayed by constitutive BK−/− mice, suggesting that compensatory pathways are active in the latter. In detrusor muscle of BK−/− but not SM-BK−/− mice, we found reduced L-type Ca2+ current density and increased expression of cAMP kinase (protein kinase A; PKA), as compared with control mice. Increased expression of PKA in BK−/− mice was accompanied by enhanced β-adrenoceptor/cAMP-mediated suppression of contractions by isoproterenol. This effect was attenuated by about 60-70% in SM-BK−/− mice. However, the Rp isomer of adenosine-3′,5′-cyclic monophosphorothioate, a blocker of PKA, only partially inhibited enhanced cAMP signaling in BK−/− detrusor muscle, suggesting the existence of additional compensatory pathways. To this end, proteome analysis of BK−/− urinary bladder tissue was performed, and revealed additional compensatory regulated proteins. Thus, constitutive and inducible deletion of BK channel activity unmasks compensatory mechanisms that are relevant for urinary bladder relaxation. |
DOI: | doi:10.1111/j.1742-4658.2009.06900.x |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1111/j.1742-4658.2009.06900.x |
| Volltext: https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1742-4658.2009.06900.x |
| DOI: https://doi.org/10.1111/j.1742-4658.2009.06900.x |
Datenträger: | Online-Ressource |
Sprache: | eng |
Bibliogr. Hinweis: | Erscheint auch als : Druck-Ausgabe: Inducible knockout mutagenesis reveals compensatorymechanisms elicited by constitutive BK channeldeficiency in overactive murine bladder. - 2009 |
Sach-SW: | cAMP/PKA signaling |
| overactive urinary bladder |
| proteomic adaptation |
| smooth muscle-specific BK channel knockout mice |
| time-dependent BK channel deletion |
K10plus-PPN: | 1681559455 |
Verknüpfungen: | → Zeitschrift |
Inducible knockout mutagenesis reveals compensatorymechanisms elicited by constitutive BK channeldeficiency in overactive murine bladder / Sproßmann, Franz [VerfasserIn]; 25 February 2009 (Online-Ressource)