Research ExplorerPublicationsInducible knockout mutagenesis reveals compensatory mechanis...

Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder.

Standard

Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder. / Sprossmann, Franz; Pankert, Patrick; Sausbier, Ulrike; Wirth, Angela; Zhou, Xiao-Bo; Madlung, Johannes; Zhao, Hong; Bucurenciu, Iancu; Jakob, Andreas; Lamkemeyer, Tobias; Neuhuber, Winfried; Offermanns, Stefan; Shipston, Michael J; Korth, Michael; Nordheim, Alfred; Ruth, Peter; Sausbier, Matthias.

In: FASEB J, Vol. 276, No. 6, 6, 2009, p. 1680-1697.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sprossmann, F, Pankert, P, Sausbier, U, Wirth, A, Zhou, X-B, Madlung, J, Zhao, H, Bucurenciu, I, Jakob, A, Lamkemeyer, T, Neuhuber, W, Offermanns, S, Shipston, MJ, Korth, M, Nordheim, A, Ruth, P & Sausbier, M 2009, 'Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder.', FASEB J, vol. 276, no. 6, 6, pp. 1680-1697. <http://www.ncbi.nlm.nih.gov/pubmed/19220851?dopt=Citation>

APA

Sprossmann, F., Pankert, P., Sausbier, U., Wirth, A., Zhou, X-B., Madlung, J., Zhao, H., Bucurenciu, I., Jakob, A., Lamkemeyer, T., Neuhuber, W., Offermanns, S., Shipston, M. J., Korth, M., Nordheim, A., Ruth, P., & Sausbier, M. (2009). Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder. FASEB J, 276(6), 1680-1697. [6]. http://www.ncbi.nlm.nih.gov/pubmed/19220851?dopt=Citation

Vancouver

Sprossmann F, Pankert P, Sausbier U, Wirth A, Zhou X-B, Madlung J et al. Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder. FASEB J. 2009;276(6):1680-1697. 6.

Bibtex

@article{f7f5c688a3214fcda5918e8fceba52bc,
title = "Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder.",
abstract = "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 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 Ca(2+) 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 beta-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.",
author = "Franz Sprossmann and Patrick Pankert and Ulrike Sausbier and Angela Wirth and Xiao-Bo Zhou and Johannes Madlung and Hong Zhao and Iancu Bucurenciu and Andreas Jakob and Tobias Lamkemeyer and Winfried Neuhuber and Stefan Offermanns and Shipston, {Michael J} and Michael Korth and Alfred Nordheim and Peter Ruth and Matthias Sausbier",
year = "2009",
language = "Deutsch",
volume = "276",
pages = "1680--1697",
journal = "FASEB J",
issn = "0892-6638",
publisher = "FASEB",
number = "6",

}

RIS

TY - JOUR

T1 - Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder.

AU - Sprossmann, Franz

AU - Pankert, Patrick

AU - Sausbier, Ulrike

AU - Wirth, Angela

AU - Zhou, Xiao-Bo

AU - Madlung, Johannes

AU - Zhao, Hong

AU - Bucurenciu, Iancu

AU - Jakob, Andreas

AU - Lamkemeyer, Tobias

AU - Neuhuber, Winfried

AU - Offermanns, Stefan

AU - Shipston, Michael J

AU - Korth, Michael

AU - Nordheim, Alfred

AU - Ruth, Peter

AU - Sausbier, Matthias

PY - 2009

Y1 - 2009

N2 - 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 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 Ca(2+) 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 beta-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.

AB - 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 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 Ca(2+) 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 beta-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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 276

SP - 1680

EP - 1697

JO - FASEB J

JF - FASEB J

SN - 0892-6638

IS - 6

M1 - 6

ER -