ArticleCirculation research2009
Smooth muscle cell alpha2delta-1 subunits are essential for vasoregulation by CaV1.2 channels.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
49 citing papers in PubMed, 77 citations in OpenAlex.
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Degradation of voltage-gated calcium channels: mechanisms and applications in neurological and cardiovascular diseases.Cell communication and signaling : CCS · 2025Review
- Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs.Open biology · 2025Review
- Altered Balance between Vasoconstrictor and Vasodilator Systems in Experimental Hypertension.Physiological research · 2024Review
- Vasodilators mobilize SK3 channels in endothelial cells to produce arterial relaxation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Modulation of CaHandbook of experimental pharmacology · 2023Article
- Oxidative Regulation of Vascular CaAntioxidants (Basel, Switzerland) · 2022Review
- Ion channel molecular complexes in vascular smooth muscle.Frontiers in physiology · 2022Review
- A paradoxical increase of force development in saphenous and tail arteries from heterozygous ANO1 knockout mice.Physiological reports · 2020Article
- Paradoxical effects of continuous high dose gabapentin treatment on autonomic dysreflexia after complete spinal cord injury.Experimental neurology · 2020Article
- Calcium signals that determine vascular resistance.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) Regulates Smooth Muscle Contractility by Modulating CaArteriosclerosis, thrombosis, and vascular biology · 2018Article
- Impaired Trafficking of β1 Subunits Inhibits BK Channels in Cerebral Arteries of Hypertensive Rats.Hypertension (Dallas, Tex. : 1979) · 2018Article
- Dynamic L-type CaBiochimica et biophysica acta. Molecular cell research · 2018Article
- PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type CaPflugers Archiv : European journal of physiology · 2018Article
- Regulation of vascular tone homeostasis by NO and HBiochemical pharmacology · 2018Review
- Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia.Channels (Austin, Tex.) · 2018Review
- Alternative Splicing of L-type CaGenes · 2017Review
- Endothelin-1 Stimulates Vasoconstriction Through Rab11A Serine 177 Phosphorylation.Circulation research · 2017Article
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
Corrections and comments
- Erratum issuedCorrection.2014
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
rationaleVoltage-dependent L-type (Ca(V)1.2) Ca(2+) channels are a heteromeric complex formed from pore-forming alpha(1) and auxiliary alpha(2)delta and beta subunits. Ca(V)1.2 channels are the principal Ca(2+) influx pathway in arterial myocytes and regulate multiple physiological functions, including contraction. The macromolecular composition of arterial myocyte Ca(V)1.2 channels remains poorly understood, with no studies having examined the molecular identity or physiological functions of alpha(2)delta subunits.
objectiveWe investigated the functional significance of alpha(2)delta subunits in myocytes of resistance-size (100 to 200 mum diameter) cerebral arteries. METHODS AND
resultsalpha(2)delta-1 was the only alpha(2)delta isoform expressed in cerebral artery myocytes. Pregabalin, an alpha(2)delta-1/-2 ligand, and an alpha(2)delta-1 antibody, inhibited Ca(V)1.2 currents in isolated myocytes. Acute pregabalin application reversibly dilated pressurized arteries. Using a novel application of surface biotinylation, data indicated that >95% of Ca(V)1.2 alpha(1) and alpha(2)delta-1 subunits were present in the arterial myocyte plasma membrane. Alpha(2)delta-1 knockdown using short hairpin RNA reduced plasma membrane-localized Ca(V)1.2 alpha(1) subunits, caused a corresponding elevation in cytosolic Ca(V)1.2 alpha(1) subunits, decreased intracellular Ca(2+) concentration, inhibited pressure-induced vasoconstriction ("myogenic tone"), and attenuated pregabalin-induced vasodilation. Prolonged (24-hour) pregabalin exposure did not alter total alpha(2)delta-1 or Ca(V)1.2 alpha(1) proteins but decreased plasma membrane expression of each subunit, which reduced myogenic tone.
conclusionsalpha(2)delta-1 is essential for plasma membrane expression of arterial myocyte Ca(V)1.2 alpha(1) subunits. alpha(2)delta-1 targeting can block Ca(V)1.2 channels directly and inhibit surface expression of Ca(V)1.2 alpha(1) subunits, leading to vasodilation. These data identify alpha(2)delta-1 as a novel molecular target in arterial myocytes, the manipulation of which regulates contractility.
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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.