TAILIEUCHUNG - Báo cáo khoa học: Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder

The large-conductance, voltage-dependent and Ca 2+ -dependent K + (BK) channel links membrane depolarization and local increases in cytosolic free Ca 2+ 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 intravesi-cal pressure and frequent micturition, which has been revealed to be a result of detrusor muscle hyperexcitability. | Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder Franz Sprossmann1 Patrick Pankert2 Ulrike Sausbier1 Angela Wirth3 Xiao-Bo Zhou4 Johannes Madlung2 Hong Zhao1 Iancu Bucurenciu1 Andreas Jakob2 Tobias Lamkemeyer2 Winfried Neuhuber5 Stefan Offermanns3 Michael J. Shipston6 Michael Korth4 Alfred Nordheim2 Peter Ruth1 and Matthias Sausbier1 1 Pharmakologie und Toxikologie Institut fur Pharmazie Universitat Tubingen Germany 2 Proteom Centrum Tubingen Interfakultares Institut fur Zellbiologie Universitat Tubingen Germany 3 Institut fur Pharmakologie Universitat Heidelberg Germany 4 Institut fur Pharmakologie fur Pharmazeuten Universitatsklinikum Hamburg-Eppendorf Germany 5 Institut fur Anatomie Universitat Erlangen-Nurnberg Germany 6 Centre for Integrative Physiology College of Medicine Veterinary Medicine University of Edinburgh UK Keywords cAMP PKA signaling overactive urinary bladder proteomic adaptation smooth muscle-specific BK channel knockout mice time-dependent BK channel deletion Correspondence P. Ruth Pharmakologie und Toxikologie Pharmazeutisches Institut Universitat Tubingen Auf der Morgenstelle 8 D-72076 Tubingen Germany Fax 49 7071 292476 Tel 49 7071 2976781 E-mail Received 1 October 2008 revised 21 December 2008 accepted 12 January 2009 doi 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 .

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