ArticleThe Journal of general physiology2013
Ca2+ oscillations, Ca2+ sensitization, and contraction activated by protein kinase C in small airway smooth muscle.
Article in The Journal of general physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
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- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
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- TRPV4 Activation during Guinea Pig Airway Smooth Muscle Contraction Promotes CaPharmaceuticals (Basel, Switzerland) · 2024Article
- Regulation of Airway Smooth Muscle Cell Proliferation by Diacylglycerol Kinase: Relevance to Airway Remodeling in Asthma.International journal of molecular sciences · 2022Article
- Role of Airway Smooth Muscle in Inflammation Related to Asthma and COPD.Advances in experimental medicine and biology · 2021Article
- Increasing Sphingolipid Synthesis Alleviates Airway Hyperreactivity.American journal of respiratory cell and molecular biology · 2020Article
- The role of diacylglycerol kinases in allergic airway disease.Current opinion in pharmacology · 2020Review
- Bile acids inhibit cholinergic constriction in proximal and peripheral airways from humans and rodents.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Airway smooth muscle tone increases actin filamentogenesis and contractile capacity.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Regulation of Myosin Light-Chain Phosphatase Activity to Generate Airway Smooth Muscle Hypercontractility.Frontiers in physiology · 2020Review
- Involvement of Allosteric Effect and KInternational journal of molecular sciences · 2018Article
- Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle.The Journal of physiology · 2017Article
- Involvement of CaInternational journal of molecular sciences · 2016Article
- Cryopreserved Human Precision-Cut Lung Slices as a Bioassay for Live Tissue Banking. A Viability Study of Bronchodilation with Bitter-Taste Receptor Agonists.American journal of respiratory cell and molecular biology · 2016Article
- Cortex phellodendri Extract Relaxes Airway Smooth Muscle.Evidence-based complementary and alternative medicine : eCAM · 2016Article
- Antagonists of the TMEM16A calcium-activated chloride channel modulate airway smooth muscle tone and intracellular calcium.Anesthesiology · 2015Article
- Selective targeting of the α5-subunit of GABAA receptors relaxes airway smooth muscle and inhibits cellular calcium handling.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Lysophosphatidic acid and apolipoprotein A1 predict increased risk of developing World Trade Center-lung injury: a nested case-control study.Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals · 2014Article
- Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity.British journal of pharmacology · 2014Article
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein kinase C (PKC) has been implicated in the regulation of smooth muscle cell (SMC) contraction and may contribute to airway hyperresponsiveness. Here, we combined optical and biochemical analyses of mouse lung slices to determine the effects of PKC activation on Ca(2+) signaling, Ca(2+) sensitivity, protein phosphorylation, and contraction in SMCs of small intrapulmonary airways. We found that 10 µM phorbol-12-myristate-13-acetate or 1 µM phorbol 12,13-dibutyrate induced repetitive, unsynchronized, and transient contractions of the SMCs lining the airway lumen. These contractions were associated with low frequency Ca(2+) oscillations in airway SMCs that resulted from Ca(2+) influx through L-type voltage-gated Ca(2+) channels and the subsequent release of Ca(2+) from intracellular stores through ryanodine receptors. Phorbol ester stimulation of lung slices in which SMC intracellular Ca(2+) concentration ([Ca(2+)](i)) was "clamped" at a high concentration induced strong airway contraction, indicating that PKC mediated sensitization of the contractile response to [Ca(2+)](i). This Ca(2+) sensitization was accompanied by phosphorylation of both the PKC-potentiated PP1 inhibitory protein of 17 kD (CPI-17) and the regulatory myosin light chain. Thrombin, like the phorbol esters, induced a strong Ca(2+) sensitization that was inhibited by the PKC inhibitor GF-109203X and also potentiated airway contraction to membrane depolarization with KCl. In conclusion, we suggest that PKC activation in small airways leads to both the generation of Ca(2+) oscillations and strong Ca(2+) sensitization; agents associated with airway inflammation, such as thrombin, may activate this pathway to sensitize airway smooth muscle to agonists that cause membrane depolarization and Ca(2+) entry and induce airway hyperresponsiveness.
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