Evidence map›Paper›PMID 37702787›Full record

ArticleThe Journal of general physiology2023

ANO1, CaV1.2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle.

Elizabeth J Akin, Joydeep Aoun, Connor Jimenez, Katie Mayne, Julius Baeck, Michael D Young, Brennan Sullivan, Kenton M Sanders, Sean M Ward, Simon Bulley and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of general physiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. CaActa physiologica (Oxford, England) · 2026
    Review
  2. Pacemaking in the lymphatic system.The Journal of physiology · 2026
    Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. CaInflammation and regeneration · 2025
    Review
  8. Article
  9. Article
  10. Roles of PDGF/PDGFR signaling in various organs.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025
    Review
  11. Effects of aging on calcium channels in skeletal muscle.Frontiers in molecular biosciences · 2025
    Review
  12. Review
  13. Review
  14. Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Elizabeth J Akin *Department of Pharmacology and Center of Biomedical Research Excellence (COBRE) for Molecular and Cellular Signal Transduction in the Cardiovascular System , Reno, NV, USA.ORCID 0000-0003-1464-7713
Joydeep Aoun *Department of Pharmacology and Center of Biomedical Research Excellence (COBRE) for Molecular and Cellular Signal Transduction in the Cardiovascular System , Reno, NV, USA.ORCID 0000-0003-1938-2830
Connor JimenezDepartment of Pharmacology and Center of Biomedical Research Excellence (COBRE) for Molecular and Cellular Signal Transduction in the Cardiovascular System , Reno, NV, USA.ORCID 0000-0001-6825-7644
Katie MayneDepartment of Pharmacology and Center of Biomedical Research Excellence (COBRE) for Molecular and Cellular Signal Transduction in the Cardiovascular System , Reno, NV, USA.ORCID 0000-0002-4555-6438
Julius BaeckDepartment of Pharmacology and Center of Biomedical Research Excellence (COBRE) for Molecular and Cellular Signal Transduction in the Cardiovascular System , Reno, NV, USA.ORCID 0000-0002-0419-2615
Michael D YoungDepartment of Pharmacology and Center of Biomedical Research Excellence (COBRE) for Molecular and Cellular Signal Transduction in the Cardiovascular System , Reno, NV, USA.ORCID 0009-0003-2312-1964
Brennan SullivanDepartment of Pharmacology and Center of Biomedical Research Excellence (COBRE) for Molecular and Cellular Signal Transduction in the Cardiovascular System , Reno, NV, USA.ORCID 0009-0008-8518-8044
Kenton M SandersDepartment of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.ORCID 0000-0002-4196-1583
Sean M WardDepartment of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.ORCID 0000-0003-0217-1535
Simon BulleyDepartment of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.ORCID 0000-0001-5985-0489
Jonathan H JaggarDepartment of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.ORCID 0000-0003-1505-3335
Scott EarleyDepartment of Pharmacology and Center of Biomedical Research Excellence (COBRE) for Molecular and Cellular Signal Transduction in the Cardiovascular System , Reno, NV, USA.ORCID 0000-0001-9560-2941
Iain A GreenwoodDepartment of Vascular Pharmacology, Molecular and Clinical Science Research Institute, St. George's University of London, London, UK.ORCID 0000-0002-0603-0492
Normand LeblancDepartment of Pharmacology and Center of Biomedical Research Excellence (COBRE) for Molecular and Cellular Signal Transduction in the Cardiovascular System , Reno, NV, USA.ORCID 0000-0002-1090-9432
University of Nevada, Reno · USUniversity of Tennessee Health Science Center · USSt George's, University of London · GB

Funding

Transgenic Animal Genotyping and Phenotyping CoreP20GM130459 · NIGMS · UNIVERSITY OF NEVADA RENO · PI Nathan Grainger · 2019 to 2026
$20.3M
TRP channels as fundamental sensors of the cerebral microcirculationR35HL155008 · NHLBI · UNIVERSITY OF ROCHESTER · PI Scott Earley · 2021 to 2026
$5.5M
Role of interstitial cells of Cajal in patterned colonic motor activityR01DK120759 · NIDDK · UNIVERSITY OF NEVADA RENO · PI Sal Baker, KENTON M SANDERS · 2019 to 2026
$3.4M
SK3 channel trafficking in endothelial cellsR01HL158846 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI JAGGAR, JONATHAN H · 2021 to 2024
$2.5M
Chloride channels in endothelial cellsR01HL166411 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI Jonathan H Jaggar · 2023 to 2026
$2.5M
PKD proteins in endothelial cellsR01HL155180 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI JAGGAR, JONATHAN H · 2021 to 2024
$2.4M
Role of ANO1 Channels and Its Regulation by PIP2 in EC-Coupling in Pulmonary Artery MyocytesR01HL146054 · NHLBI · UNIVERSITY OF NEVADA RENO · PI EARLEY, SCOTT, LEBLANC, NORMAND · 2019 to 2022
$2.0M
British Heart Foundation FS/18/41/33762NHLBI NIH HHS R01 HL146054NHLBI NIH HHS R01 HL155180NHLBI NIH HHS R01 HL158846NHLBI NIH HHS R01 HL166411NHLBI NIH HHS R35 HL155008NIDDK NIH HHS R01 DK120759NIGMS NIH HHS P20 GM130459NIH HHS R01HL146054
6 · The paper itself

Abstract

Pulmonary arterial (PA) smooth muscle cells (PASMC) generate vascular tone in response to agonists coupled to Gq-protein receptor signaling. Such agonists stimulate oscillating calcium waves, the frequency of which drives the strength of contraction. These Ca2+ events are modulated by a variety of ion channels including voltage-gated calcium channels (CaV1.2), the Tmem16a or Anoctamin-1 (ANO1)-encoded calcium-activated chloride (CaCC) channel, and Ca2+ release from the sarcoplasmic reticulum through inositol-trisphosphate receptors (IP3R). Although these calcium events have been characterized, it is unclear how these calcium oscillations underly a sustained contraction in these muscle cells. We used smooth muscle-specific ablation of ANO1 and pharmacological tools to establish the role of ANO1, CaV1.2, and IP3R in the contractile and intracellular Ca2+ signaling properties of mouse PA smooth muscle expressing the Ca2+ biosensor GCaMP3 or GCaMP6. Pharmacological block or genetic ablation of ANO1 or inhibition of CaV1.2 or IP3R, or Ca2+ store depletion equally inhibited 5-HT-induced tone and intracellular Ca2+ waves. Coimmunoprecipitation experiments showed that an anti-ANO1 antibody was able to pull down both CaV1.2 and IP3R. Confocal and superresolution nanomicroscopy showed that ANO1 coassembles with both CaV1.2 and IP3R at or near the plasma membrane of PASMC from wild-type mice. We conclude that the stable 5-HT-induced PA contraction results from the integration of stochastic and localized Ca2+ events supported by a microenvironment comprising ANO1, CaV1.2, and IP3R. In this model, ANO1 and CaV1.2 would indirectly support cyclical Ca2+ release events from IP3R and propagation of intracellular Ca2+ waves.

Indexed as

CalciumHypertension, PulmonaryAnimalsAnoctamin-1MiceMuscle, SmoothSerotoninAnoctamin-1CalciumSerotonin

Identifiers

PMID37702787
PMCPMC10499037
OpenAlexW4386704274

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.