ArticleAmerican journal of physiology. Cell physiology2014
Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein kinase C in guinea pig urinary bladder smooth muscle.
Article in American journal of physiology. Cell physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Machine Learning on a Genome-wide Association Study to Predict Late Genitourinary Toxicity After Prostate Radiation Therapy.International journal of radiation oncology, biology, physics · 2018Trial
- Smooth muscle of the lower urinary tract: BK-RyR coupling in physiology and pathophysiology.Journal of muscle research and cell motility · 2025Review
- In Silico Electrophysiological Investigation of Transient Receptor Potential Melastatin-4 Ion Channel Biophysics to Study Detrusor Overactivity.International journal of molecular sciences · 2024Article
- Carotid body chemoreceptors: physiology, pathology, and implications for health and disease.Physiological reviews · 2021Review
- Age-dependent decrease in TRPM4 channel expression but not trafficking alters urinary bladder smooth muscle contractility.Physiological reports · 2021Article
- Urinary bladder smooth muscle ion channels: expression, function, and regulation in health and disease.American journal of physiology. Renal physiology · 2020Review
- A Novel in situ Approach to Studying Detrusor Smooth Muscle Cells in Mice.Scientific reports · 2020Article
- TRPM4 channel inhibitors 9-phenanthrol and glibenclamide differentially decrease guinea pig detrusor smooth muscle whole-cell cation currents and phasic contractions.American journal of physiology. Cell physiology · 2020Article
- 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
- The Dome Wall of Bladder Acts as a Pacemaker Site in Detrusor Instability in Rats.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels.Frontiers in physiology · 2017Review
- Big-conductance CaChannels (Austin, Tex.) · 2016Review
- Regulation of urinary bladder function by protein kinase C in physiology and pathophysiology.BMC urology · 2015Review
- Changes in the glucocorticoid receptor and Ca²⁺/calreticulin-dependent signalling pathway in the medial prefrontal cortex of rats with post-traumatic stress disorder.Journal of molecular neuroscience : MN · 2015Article
- Protein kinase C modulates frequency of micturition and non-voiding contractions in the urinary bladder via neuronal and myogenic mechanisms.BMC urology · 2015Article
- Functional link between muscarinic receptors and large-conductance Ca2+ -activated K+ channels in freshly isolated human detrusor smooth muscle cells.Pflugers Archiv : European journal of physiology · 2015Article
- Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology.American journal of physiology. Regulatory, integrative and comparative physiology · 2014Review
- Prostaglandin E2 excitatory effects on guinea pig urinary bladder smooth muscle: a novel regulatory mechanism mediated by large-conductance voltage- and Ca2+-activated K+ channels.European journal of pharmacology · 2014Article
- BK channel activators and their therapeutic perspectives.Frontiers in physiology · 2014Review
- Functional insights into modulation of BKCa channel activity to alter myometrial contractility.Frontiers in physiology · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Large-conductance voltage- and Ca(2+)-activated K(+) (BK) channels are critical regulators of detrusor smooth muscle (DSM) excitability and contractility. PKC modulates the contraction of DSM and BK channel activity in non-DSM cells; however, the cellular mechanism regulating the PKC-BK channel interaction in DSM remains unknown. We provide a novel mechanistic insight into BK channel regulation by PKC in DSM. We used patch-clamp electrophysiology, live-cell Ca(2+) imaging, and functional studies of DSM contractility to elucidate BK channel regulation by PKC at cellular and tissue levels. Voltage-clamp experiments showed that pharmacological activation of PKC with PMA inhibited the spontaneous transient BK currents in native freshly isolated guinea pig DSM cells. Current-clamp recordings revealed that PMA significantly depolarized DSM membrane potential and inhibited the spontaneous transient hyperpolarizations in DSM cells. The PMA inhibitory effects on DSM membrane potential were completely abolished by the selective BK channel inhibitor paxilline. Activation of PKC with PMA did not affect the amplitude of the voltage-step-induced whole cell steady-state BK current or the single BK channel open probability (recorded in cell-attached mode) upon inhibition of all major Ca(2+) sources for BK channel activation with thapsigargin, ryanodine, and nifedipine. PKC activation with PMA elevated intracellular Ca(2+) levels in DSM cells and increased spontaneous phasic and nerve-evoked contractions of DSM isolated strips. Our results support the concept that PKC activation leads to a reduction of BK channel activity in DSM via a Ca(2+)-dependent mechanism, thus increasing DSM contractility.
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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.