ArticlePloS one2013
Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca(2+)-activated K(+) channels.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 49 citations in OpenAlex.
- Ion Channels as Therapeutic Targets in Overactive Bladder: A Narrative Review of Mechanisms, Translational Evidence, and Current Gaps.Lower urinary tract symptoms · 2026Review
- Cells and ionic conductances contributing to spontaneous activity in bladder and urethral smooth muscle.The Journal of physiology · 2026Review
- Smooth muscle of the lower urinary tract: BK-RyR coupling in physiology and pathophysiology.Journal of muscle research and cell motility · 2025Review
- Activation mechanism and novel binding sites of the BKLife science alliance · 2024Article
- Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse Models.International journal of molecular sciences · 2023Article
- Novel Thioxothiazolo[3,4-ACS medicinal chemistry letters · 2022Article
- Gene Therapy for Overactive Bladder: A Review of BK-Channel α-Subunit Gene Transfer.Therapeutics and clinical risk management · 2021Review
- The intracellular CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Lower urinary tract dysfunction in common neurological diseases.Turkish journal of urology · 2020Review
- Urinary bladder smooth muscle ion channels: expression, function, and regulation in health and disease.American journal of physiology. Renal physiology · 2020Review
- Preparation and Utilization of Freshly Isolated Human Detrusor Smooth Muscle Cells for Characterization of 9-Phenanthrol-Sensitive Cation Currents.Journal of visualized experiments : JoVE · 2020Article
- Detrusor Smooth Muscle KFrontiers in physiology · 2020Review
- Article
- Altered detrusor contractility and voiding patterns in mice lacking the mechanosensitive TREK-1 channel.BMC urology · 2019Article
- Effect of high-fat diet-induced obesity on the small-conductance CaInternational urology and nephrology · 2019Article
- Involvement of TRPM4 in detrusor overactivity following spinal cord transection in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- The role of the mucosa in modulation of evoked responses in the spinal cord injured rat bladder.Neurourology and urodynamics · 2018Article
- A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle.PloS one · 2018Article
- Regulation of transient receptor potential melastatin 4 channel by sarcoplasmic reticulum inositol trisphosphate receptors: Role in human detrusor smooth muscle function.Channels (Austin, Tex.) · 2017Article
- Expression and function of the small-conductance CaInternational urology and nephrology · 2017Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson's disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO), which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM) large conductance Ca(2+)-activated K(+) (BK) channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR), perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs) in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.
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