ArticleProceedings of the National Academy of Sciences of the United States of America2015
G-protein βγ subunits are positive regulators of Kv7.4 and native vascular Kv7 channel activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
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- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Cholesterol and Cholesterol-Derived Molecules Differentially Modulate Neuronal Kv7.2/7.3 Channels.Archiv der Pharmazie · 2026Article
- Two-step voltage-sensor activation of the human KNature communications · 2026Article
- Sphingosine-1-phosphate activates LRRC8 volume-regulated anion channels through Gβγ signalling.The Journal of physiology · 2025Article
- G protein βγ regulation of KCNQ-encoded voltage-dependent K channels.Frontiers in physiology · 2024Review
- Inhibition of voltage-dependent KThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Physiology and Proteomic Basis of Lung Adaptation to High-Altitude Hypoxia in Tibetan Sheep.Animals : an open access journal from MDPI · 2022Article
- Sexual dimorphism in prostacyclin-mimetic responses within rat mesenteric arteries: A novel role for KBritish journal of pharmacology · 2022Article
- KAmerican journal of physiology. Renal physiology · 2022Article
- Involvement of Gi protein-dependent BKNaunyn-Schmiedeberg's archives of pharmacology · 2020Article
- The Functional Availability of Arterial Kv7 Channels Is Suppressed Considerably by Large-Conductance Calcium-Activated Potassium Channels in 2- to 3-Month Old but Not in 10- to 15-Day Old Rats.Frontiers in physiology · 2020Article
- Cyclic AMP-Dependent Regulation of Kv7 Voltage-Gated Potassium Channels.Frontiers in physiology · 2020Review
- The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes.Frontiers in cellular neuroscience · 2020Review
- Mechanisms of cannabinoid CBEBioMedicine · 2019Article
- Kv7.4 Channel Contribute to Projection-Specific Auto-Inhibition of Dopamine Neurons in the Ventral Tegmental Area.Frontiers in cellular neuroscience · 2019Article
- The Gβ1 and Gβ3 Subunits Differentially Regulate Rat Vascular Kv7 Channels.Frontiers in physiology · 2019Article
- Investigating the Role of G Protein βγ in Kv7-Dependent Relaxations of the Rat Vasculature.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Inhibition of voltage-dependent KThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2018Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Kv7.4 channels are a crucial determinant of arterial diameter both at rest and in response to endogenous vasodilators. However, nothing is known about the factors that ensure effective activity of these channels. We report that G-protein βγ subunits increase the amplitude and activation rate of whole-cell voltage-dependent K(+) currents sensitive to the Kv7 blocker linopirdine in HEK cells heterologously expressing Kv7.4, and in rat renal artery myocytes. In excised patch recordings, Gβγ subunits (2-250 ng /mL) enhanced the open probability of Kv7.4 channels without changing unitary conductance. Kv7 channel activity was also augmented by stimulation of G-protein-coupled receptors. Gallein, an inhibitor of Gβγ subunits, prevented these stimulatory effects. Moreover, gallein and two other structurally different Gβγ subunit inhibitors (GRK2i and a β-subunit antibody) abolished Kv7 channel currents in the absence of either Gβγ subunit enrichment or G-protein-coupled receptor stimulation. Proximity ligation assay revealed that Kv7.4 and Gβγ subunits colocalized in HEK cells and renal artery smooth muscle cells. Gallein disrupted this colocalization, contracted whole renal arteries to a similar degree as the Kv7 inhibitor linopirdine, and impaired isoproterenol-induced relaxations. Furthermore, mSIRK, which disassociates Gβγ subunits from α subunits without stimulating nucleotide exchange, relaxed precontracted arteries in a linopirdine-sensitive manner. These results reveal that Gβγ subunits are fundamental for Kv7.4 activation and crucial for vascular Kv7 channel activity, which has major consequences for the regulation of arterial tone.
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