ArticleProceedings of the National Academy of Sciences of the United States of America2010
Thromboxane A2 receptor and MaxiK-channel intimate interaction supports channel trans-inhibition independent of G-protein activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- The scale of zebrafish pectoral fin buds is determined by intercellular K+ levels and consequent Ca2+-mediated signaling via retinoic acid regulation of Rcan2 and Kcnk5b.PLoS biology · 2024Article
- Homocysteine alters vasoreactivity of human internal mammary artery by affecting the KAnnals of translational medicine · 2021Article
- Application of Machine-Learning Methods to Recognize mitoBK Channels from Different Cell Types Based on the Experimental Patch-Clamp Results.International journal of molecular sciences · 2021Article
- Article
- MitoBKThe Journal of physiology · 2019Article
- Heme Oxygenases in Cardiovascular Health and Disease.Physiological reviews · 2016Review
- Data supporting characterization of CLIC1, CLIC4, CLIC5 and DmCLIC antibodies and localization of CLICs in endoplasmic reticulum of cardiomyocytes.Data in brief · 2016Article
- Tungstate-targeting of BKαβ1 channels tunes ERK phosphorylation and cell proliferation in human vascular smooth muscle.PloS one · 2015Article
- BK channels: multiple sensors, one activation gate.Frontiers in physiology · 2015Review
- 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
- Vascular targets for cannabinoids: animal and human studies.British journal of pharmacology · 2014Review
- MitoBK(Ca) is encoded by the Kcnma1 gene, and a splicing sequence defines its mitochondrial location.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Transduction of voltage and Ca2+ signals by Slo1 BK channels.Physiology (Bethesda, Md.) · 2013Review
- The β1-subunit of the MaxiK channel associates with the thromboxane A2 receptor and reduces thromboxane A2 functional effects.The Journal of biological chemistry · 2013Article
- New insights into structural determinants for prostanoid thromboxane A2 receptor- and prostacyclin receptor-G protein coupling.Molecular and cellular biology · 2013Article
- Function and regulation of large conductance Ca(2+)-activated K+ channel in vascular smooth muscle cells.Drug discovery today · 2012Review
- Visualization and quantification of cardiac mitochondrial protein clusters with STED microscopy.Mitochondrion · 2012Article
- Metal-driven operation of the human large-conductance voltage- and Ca2+-dependent potassium channel (BK) gating ring apparatus.The Journal of biological chemistry · 2011Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Large conductance voltage- and calcium-activated potassium channels (MaxiK, BK(Ca)) are well known for sustaining cerebral and coronary arterial tone and for their linkage to vasodilator β-adrenergic receptors. However, how MaxiK channels are linked to counterbalancing vasoconstrictor receptors is unknown. Here, we show that vasopressive thromboxane A2 receptors (TP) can intimately couple with and inhibit MaxiK channels. Activation of the receptor with its agonist trans-inhibits MaxiK independently of G-protein activation. This unconventional mechanism is supported by independent lines of evidence: (i) inhibition of MaxiK current by thromboxane A2 mimetic, U46619, occurs even when G-protein activity is suppressed; (ii) MaxiK and TP physically associate and display a high degree of proximity; and (iii) Förster resonance energy transfer occurs between fluorescently labeled MaxiK and TP, supporting a direct interaction. The molecular mechanism of MaxiK-TP intimate interaction involves the receptor's first intracellular loop and C terminus, and it entails the voltage-sensing conduction cassette of MaxiK channel. Further, physiological evidence of MaxiK-TP physical interaction is given in human coronaries and rat aorta, and by confirming TP role (with antagonist SQ29,548) in the U46619-induced MaxiK inhibition in human coronaries. We propose that vasoconstrictor TP receptor and MaxiK-channel direct interaction facilitates G-protein-independent TP to MaxiK trans-inhibition, which would promote vasoconstriction.
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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.