ArticleMolecular pharmacology2016
Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents.
Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 61 citations in OpenAlex.
- KCommunications medicine · 2026Article
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- HBasic research in cardiology · 2025Article
- Sexually dimorphic mechanisms of HJournal of applied physiology (Bethesda, Md. : 1985) · 2025Article
- KAddiction biology · 2024Article
- Inhibition of voltage-dependent KThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- HumanJournal of neurophysiology · 2022Article
- Kv7 Channels in Cyclic-Nucleotide Dependent Relaxation of Rat Intra-Pulmonary Artery.Biomolecules · 2022Article
- Modeling the kinetics of heteromeric potassium channels.Frontiers in cellular neuroscience · 2022Article
- Kv7 channel trafficking by the microtubule network in vascular smooth muscle.Acta physiologica (Oxford, England) · 2021Review
- PKCζ-NADPH Oxidase-PKCα Dependent Kv1.5 Phosphorylation by Endothelin-1 Modulates Nav1.5-NCX1-Cav1.2 Axis in Stimulating CaCell biochemistry and biophysics · 2021Article
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- Aging Affects KFrontiers in physiology · 2021Article
- Kv7 Channels and Excitability Disorders.Handbook of experimental pharmacology · 2021Article
- Vascular Kv7 channels control intracellular CaCell calcium · 2020Article
- Acetaminophen (Paracetamol) Metabolites Induce Vasodilation and Hypotension by Activating Kv7 Potassium Channels Directly and Indirectly.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Pirfenidone Is a Vasodilator: Involvement of KFrontiers in pharmacology · 2020Article
- Activation of Inward Rectifier KBioMed research international · 2020Article
- Kv7 Channels in Lung Diseases.Frontiers in physiology · 2020Review
- Heteromeric Channels Formed From Alternating Kv7.4 and Kv7.5 α-Subunits Display Biophysical, Regulatory, and Pharmacological Characteristics of Smooth Muscle M-Currents.Frontiers in physiology · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K(+) currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 >> Kv7.4/Kv7.5 > Kv7.4.
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