ArticleAmerican journal of physiology. Cell physiology2012
Inhibition of phosphodiesterases relaxes detrusor smooth muscle via activation of the large-conductance voltage- and Ca²⁺-activated K⁺ channel.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- In Silico Electrophysiological Investigation of Transient Receptor Potential Melastatin-4 Ion Channel Biophysics to Study Detrusor Overactivity.International journal of molecular sciences · 2024Article
- 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
- Acute radiation impacts contractility of guinea-pig bladder strips affecting mucosal-detrusor interactions.PloS one · 2018Article
- Large conductance voltage and CaAmerican journal of translational research · 2017Article
- 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
- Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology.American journal of physiology. Regulatory, integrative and comparative physiology · 2014Review
- Microvascular dysfunction and efficacy of PDE5 inhibitors in BPH-LUTS.Nature reviews. Urology · 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
- Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein kinase C in guinea pig urinary bladder smooth muscle.American journal of physiology. Cell physiology · 2014Article
- Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels.American journal of physiology. Cell physiology · 2014Article
- Activation of muscarinic M3 receptors inhibits large-conductance voltage- and Ca2+-activated K+ channels in rat urinary bladder smooth muscle cells.American journal of physiology. Cell physiology · 2013Article
- Functional BK channels facilitate the β3-adrenoceptor agonist-mediated relaxation of nerve-evoked contractions in rat urinary bladder smooth muscle isolated strips.European journal of pharmacology · 2013Article
- Single-channel biophysical and pharmacological characterizations of native human large-conductance calcium-activated potassium channels in freshly isolated detrusor smooth muscle cells.Pflugers Archiv : European journal of physiology · 2013Article
- Novel role for the transient potential receptor melastatin 4 channel in guinea pig detrusor smooth muscle physiology.American journal of physiology. Cell physiology · 2013Article
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- Selective inhibition of phosphodiesterase 1 relaxes urinary bladder smooth muscle: role for ryanodine receptor-mediated BK channel activation.American journal of physiology. Cell physiology · 2012Article
- Constitutively active phosphodiesterase activity regulates urinary bladder smooth muscle function: critical role of KCa1.1 channel.American journal of physiology. Renal physiology · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Detrusor smooth muscle (DSM) exhibits increased spontaneous phasic contractions under pathophysiological conditions such as detrusor overactivity (DO). Our previous studies showed that activation of cAMP signaling pathways reduces DSM contractility by increasing the large-conductance voltage- and Ca(2+)-activated K(+) (BK) channel activity. Here, we tested the hypothesis whether inhibition of phosphodiesterases (PDEs) can reduce guinea pig DSM excitability and contractility by increasing BK channel activity. Utilizing isometric tension recordings of DSM isolated strips and the perforated patch-clamp technique on freshly isolated DSM cells, we examined the mechanism of DSM relaxation induced by PDE inhibition. Inhibition of PDEs by 3-isobutyl-1-methylxanthine (IBMX), a nonselective PDE inhibitor, significantly reduced DSM spontaneous and carbachol-induced contraction amplitude, frequency, duration, muscle force integral, and tone in a concentration-dependent manner. IBMX significantly reduced electrical field stimulation-induced contractions of DSM strips. Blocking BK channels with paxilline diminished the inhibitory effects of IBMX on DSM contractility, indicating a role for BK channels in DSM relaxation mediated by PDE inhibition. IBMX increased the transient BK currents (TBKCs) frequency by ∼3-fold without affecting the TBKCs amplitude. IBMX increased the frequency of the spontaneous transient hyperpolarizations by ∼2-fold and hyperpolarized the DSM cell resting membrane potential by ∼6 mV. Blocking the BK channels with paxilline abolished the IBMX hyperpolarizing effects. Under conditions of blocked Ca(2+) sources for BK channel activation, IBMX did not affect the depolarization-induced steady-state whole cell BK currents. Our data reveal that PDE inhibition with IBMX relaxes guinea pig DSM via TBKCs activation and subsequent DSM cell membrane hyperpolarization.
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