ArticleThe Journal of biological chemistry2008
M2 muscarinic receptors induce airway smooth muscle activation via a dual, Gbetagamma-mediated inhibition of large conductance Ca2+-activated K+ channel activity.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.PloS one · 2011Pooled it
- Unravelling the Role of Post-Junctional M2 Muscarinic Receptors in Cholinergic Nerve-Mediated Contractions of Airway Smooth Muscle.International journal of molecular sciences · 2025Review
- Investigation of Potential Drug Targets Involved in Inflammation Contributing to Alzheimer's Disease Progression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Calcium-Dependent Regulation of the Neuronal Glycine Transporter GlyT2 by M2 Muscarinic Acetylcholine Receptors.Neurochemical research · 2022Article
- Roles of LRRC26 as an auxiliary γ1-subunit of large-conductance CaAmerican journal of physiology. Lung cellular and molecular physiology · 2020Article
- cAMP guided his way: a life for G protein-mediated signal transduction and molecular pharmacology-tribute to Karl H. Jakobs.Naunyn-Schmiedeberg's archives of pharmacology · 2019Review
- Relaxant Action of Diclofenac Sodium on Mouse Airway Smooth Muscle.Frontiers in pharmacology · 2019Article
- Inflammation leads through PGE/EPEMBO molecular medicine · 2018Article
- Chloroform Extract ofEvidence-based complementary and alternative medicine : eCAM · 2017Article
- G Protein-Coupled Receptors (GPCRs) in Alzheimer's Disease: A Focus on BACE1 Related GPCRs.Frontiers in aging neuroscience · 2016Review
- Membrane potential and Ca2+ concentration dependence on pressure and vasoactive agents in arterial smooth muscle: A model.The Journal of general physiology · 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
- Tungstate-targeting of BKαβ1 channels tunes ERK phosphorylation and cell proliferation in human vascular smooth muscle.PloS one · 2015Article
- Article
- The angiotensin II type 1 receptor (AT1R) closely interacts with large conductance voltage- and Ca2+-activated K+ (BK) channels and inhibits their activity independent of G-protein activation.The Journal of biological chemistry · 2014Article
- MaxiK channel and cell signalling.Pflugers Archiv : European journal of physiology · 2014Review
- Functional insights into modulation of BKCa channel activity to alter myometrial contractility.Frontiers in physiology · 2014Review
- Treatment of experimental asthma using a single small molecule with anti-inflammatory and BK channel-activating properties.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- 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
- Noradrenaline stimulates cell proliferation by suppressing potassium channels via G(i/o) -protein-coupled α(1B) -adrenoceptors in human osteoblasts.British journal of pharmacology · 2013Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Airway smooth muscle is richly endowed with muscarinic receptors of the M(2) and M(3) subtype. Stimulation of these receptors inhibits large conductance calcium-activated K(+) (BK) channels, a negative feed back regulator, in a pertussis toxin-sensitive manner and thus facilitates contraction. The underlying mechanism, however, is unknown. We therefore studied the activity of bovine trachea BK channels in HEK293 cells expressing the M(2) or M(3) receptor (M(2)R or M(3)R). In M(2)R- but not M(3)R-expressing cells, maximal effective concentrations of carbamoylcholine (CCh) inhibited whole cell BK currents by 53%. This M(2)R-induced inhibition was abolished by pertussis toxin treatment or overexpression of the Gbetagamma scavenger transducin-alpha. In inside-out patches, direct application of 300 nm purified Gbetagamma decreased channel open probability by 55%. The physical interaction of Gbetagamma with BK channels was confirmed by co-immunoprecipitation. Interestingly, inhibition of phospholipase C as well as protein kinase C activities also reversed the CCh effect but to a smaller (approximately 20%) extent. Mouse tracheal cells responded similarly to CCh, purified Gbetagamma and phospholipase C/protein kinase C inhibition as M(2)R-expressing HEK293 cells. Our results demonstrate that airway M(2)Rs inhibit BK channels by a dual, Gbetagamma-mediated mechanism, a direct membrane-delimited interaction, and the activation of the phospholipase C/protein kinase C pathway.
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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.