ArticleFrontiers in physiology2013
Functional effects of KCNQ K(+) channels in airway smooth muscle.
Article in Frontiers in physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 2023Review
- Chemical modulation of Kv7 potassium channels.RSC medicinal chemistry · 2021Review
- Kv7 Channels and Excitability Disorders.Handbook of experimental pharmacology · 2021Article
- Functional responses of the hippocampus to hyperexcitability depend on directed, neuron-specific KCNQ2 KHippocampus · 2020Article
- Cyclic AMP-Dependent Regulation of Kv7 Voltage-Gated Potassium Channels.Frontiers in physiology · 2020Review
- Detrusor Smooth Muscle KFrontiers in physiology · 2020Review
- Kv7 Channels in Lung Diseases.Frontiers in physiology · 2020Review
- KCNQ/M-channels regulate mouse vagal bronchopulmonary C-fiber excitability and cough sensitivity.JCI insight · 2019Article
- Discovery of Novel Retigabine Derivatives as Potent KCNQ4 and KCNQ5 Channel Agonists with Improved Specificity.ACS medicinal chemistry letters · 2019Article
- Voltage effects on muscarinic acetylcholine receptor-mediated contractions of airway smooth muscle.Physiological reports · 2018Article
- Mechanisms of PKA-Dependent Potentiation of Kv7.5 Channel Activity in Human Airway Smooth Muscle Cells.International journal of molecular sciences · 2018Article
- KThe Journal of pharmacology and experimental therapeutics · 2018Article
- Vascular Smooth Muscle as a Target for Novel Therapeutics.Current diabetes reports · 2015Review
- Western blot analysis of BK channel β1-subunit expression should be interpreted cautiously when using commercially available antibodies.Physiological reports · 2014Article
- Differential activation of vascular smooth muscle Kv7.4, Kv7.5, and Kv7.4/7.5 channels by ML213 and ICA-069673.Molecular pharmacology · 2014Article
- Evolutionary analysis of voltage-gated potassium channels by Bayes method.Journal of molecular neuroscience : MN · 2014Article
- KCNQ (Kv7) potassium channel activators as bronchodilators: combination with a β2-adrenergic agonist enhances relaxation of rat airways.American journal of physiology. Lung cellular and molecular physiology · 2014Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
KCNQ (Kv7) channels underlie a voltage-gated K(+) current best known for control of neuronal excitability, and its inhibition by Gq/11-coupled, muscarinic signaling. Studies have indicated expression of KCNQ channels in airway smooth muscle (ASM), a tissue that is predominantly regulated by muscarinic receptor signaling. Therefore, we investigated the function of KCNQ channels in rodent ASM and their interplay with Gq/11-coupled M3 muscarinic receptors. Perforated-patch clamp of dissociated ASM cells detected a K(+) current inhibited by the KCNQ antagonist, XE991, and augmented by the specific agonist, flupirtine. KCNQ channels begin to activate at voltages near resting potentials for ASM cells, and indeed XE991 depolarized resting membrane potentials. Muscarinic receptor activation inhibited KCNQ current weakly (~20%) at concentrations half-maximal for contractions. Thus, we were surprised to see that KCNQ had no affect on membrane voltage or muscle contractility following muscarinic activation. Further, M3 receptor-specific antagonist J104129 fumarate alone did not reveal KCNQ effects on muscarinic evoked depolarization or contractility. However, a role for KCNQ channels was revealed when BK-K(+) channel activities are reduced. While KCNQ channels do control resting potentials, they appear to play a redundant role with BK calcium-activated K(+) channels during ASM muscarinic signaling. In contrast to effect of antagonist, we observe that KCNQ agonist flupirtine caused a significant hyperpolarization and reduced contraction in vitro irrespective of muscarinic activation. Using non-invasive whole animal plethysmography, the clinically approved KCNQ agonist retigabine caused a transient reduction in indexes of airway resistance in both wild type and BK β1 knockout (KO) mice treated with the muscarinic agonist. These findings indicate that KCNQ channels can be recruited via agonists to oppose muscarinic evoked contractions and may be of therapeutic value as bronchodilators.
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