ArticleThe FEBS journal2009
Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder.
Article in The FEBS journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Smooth muscle of the lower urinary tract: BK-RyR coupling in physiology and pathophysiology.Journal of muscle research and cell motility · 2025Review
- The intracellular CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Urinary bladder smooth muscle ion channels: expression, function, and regulation in health and disease.American journal of physiology. Renal physiology · 2020Review
- Paxilline Prevents the Onset of Myotonic Stiffness in Pharmacologically Induced Myotonia: A Preclinical Investigation.Frontiers in physiology · 2020Article
- Review
- Article
- Characterisation of the Ral GTPase inhibitor RBC8 in human and mouse platelets.Cellular signalling · 2019Article
- The large-conductance voltage- and CaThe Journal of physiology · 2018Article
- A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle.PloS one · 2018Article
- Generation of Kcnma1fl-tdTomato, a conditional deletion of the BK channel α subunit in mouse.Physiological reports · 2015Article
- Constitutive PKA activity is essential for maintaining the excitability and contractility in guinea pig urinary bladder smooth muscle: role of the BK channel.American journal of physiology. Cell physiology · 2014Article
- Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2014Article
- Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology.American journal of physiology. Regulatory, integrative and comparative physiology · 2014Review
- Smooth muscle BK channel activity influences blood pressure independent of vascular tone in mice.The Journal of physiology · 2014Article
- The pharmacological rationale for combining muscarinic receptor antagonists and β-adrenoceptor agonists in the treatment of airway and bladder disease.Current opinion in pharmacology · 2014Review
- BK channel-mediated relaxation of urinary bladder smooth muscle: a novel paradigm for phosphodiesterase type 4 regulation of bladder function.The Journal of pharmacology and experimental therapeutics · 2014Article
- The regulation of BK channel activity by pre- and post-translational modifications.Frontiers in physiology · 2014Review
- KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury.PloS one · 2014Article
- BK channel activators and their therapeutic perspectives.Frontiers in physiology · 2014Review
- Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.