ArticleThe Journal of pharmacology and experimental therapeutics2012
Pharmacological activation of small conductance calcium-activated potassium channels with naphtho[1,2-d]thiazol-2-ylamine decreases guinea pig detrusor smooth muscle excitability and contractility.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 47 citations in OpenAlex.
- Role of detrusor PDGFRαScientific reports · 2022Article
- Imatinib Mesylate Reduces Voiding Frequency in Female Mice With Acute Cyclophosphamide-Induced Cystitis.Frontiers in systems neuroscience · 2022Article
- Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity.Scientific reports · 2021Article
- Age-dependent decrease in TRPM4 channel expression but not trafficking alters urinary bladder smooth muscle contractility.Physiological reports · 2021Article
- Calcium-Activated KHandbook of experimental pharmacology · 2021Article
- Attenuated regulatory function of the small-conductance CaInternational urology and nephrology · 2020Article
- Urinary bladder smooth muscle ion channels: expression, function, and regulation in health and disease.American journal of physiology. Renal physiology · 2020Review
- 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
- Properties of single-channel and whole cell ClAmerican journal of physiology. Cell physiology · 2019Article
- Involvement of transient receptor potential melastatin 4 channels in the resting membrane potential setting and cholinergic contractile responses in mouse detrusor and ileal smooth muscles.The Journal of veterinary medical science · 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
- A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle.PloS one · 2018Article
- Pharmacologic targeting of endothelial CaChannels (Austin, Tex.) · 2018Review
- Expression and function of the small-conductance CaInternational urology and nephrology · 2017Article
- Partial bladder outlet obstruction is associated with decreased expression and function of the small-conductance CaInternational urology and nephrology · 2017Article
- A simple, rapid, and efficient method for isolating detrusor for the culture of bladder smooth muscle cells.International urology and nephrology · 2016Article
- UTP activates small-conductance Ca2+-activated K+ channels in murine detrusor PDGFRα+ cells.American journal of physiology. Renal 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
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Small conductance Ca²⁺-activated K⁺ (SK) and intermediate conductance Ca(2+)-activated K⁺ (IK) channels are thought to be involved in detrusor smooth muscle (DSM) excitability and contractility. Using naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a novel and highly specific SK/IK channel activator, we investigated whether pharmacological activation of SK/IK channels reduced guinea pig DSM excitability and contractility. We detected the expression of all known isoforms of SK (SK1-SK3) and IK channels at mRNA and protein levels in DSM by single-cell reverse transcription-polymerase chain reaction and Western blot. Using the perforated patch-clamp technique on freshly isolated DSM cells, we observed that SKA-31 (10 μM) increased SK currents, which were blocked by apamin (1 μM), a selective SK channel inhibitor. In current-clamp mode, SKA-31 (10 μM) hyperpolarized the cell resting membrane potential, which was blocked by apamin (1 μM) but not by 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) (1 μM), a selective IK channel inhibitor. SKA-31 (10 nM-10 μM) significantly inhibited the spontaneous phasic contraction amplitude, frequency, duration, and muscle force in DSM isolated strips. The SKA-31 inhibitory effects on DSM contractility were blocked by apamin (1 μM) but not by TRAM-34 (1 μM), which did not per se significantly affect DSM spontaneous contractility. SK channel activation with SKA-31 reduced contractions evoked by electrical field stimulation. SKA-31 effects were reversible upon washout. In conclusion, SK channels, but not IK channels, mediate SKA-31 effects in guinea pig DSM. Pharmacological activation of SK channels reduces DSM excitability and contractility and therefore may provide a novel therapeutic approach for controlling bladder dysfunction.
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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.