Evidence map›Paper›PMID 27859335›Full record

ArticleThe Journal of physiology2017

Extracellular protons enable activation of the calcium-dependent chloride channel TMEM16A.

Silvia Cruz-Rangel, José J De Jesús-Pérez, Iván A Aréchiga-Figueroa, Aldo A Rodríguez-Menchaca, Patricia Pérez-Cornejo, H Criss Hartzell, Jorge Arreola

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

26 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Review
  3. Calcium-activated chloride channel TMEM16A opens via pi-helical transition in transmembrane segment 4.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Distinct modulation of calcium-activated chloride channel TMEM16A by drug-binding sites.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. The role of anoctamin 1 in liver disease.Journal of cellular and molecular medicine · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Polymodal Control of TMEM16x Channels and Scramblases.International journal of molecular sciences · 2022
    Review
  11. Article
  12. Article
  13. Article
  14. The taming of a scramblase.The Journal of general physiology · 2021
    Article
  15. Article
  16. Review
  17. Review
  18. Structure-Function of TMEM16 Ion Channels and Lipid Scramblases.Advances in experimental medicine and biology · 2021
    Article
  19. Allosteric modulation of alternatively spliced CaProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Silvia Cruz-RangelPhysics Institute, Universidad Autónoma de San Luis Potosí, Ave. Dr. Manuel Nava #6, San Luis Potosí, SLP, 78290, México.
José J De Jesús-PérezPhysics Institute, Universidad Autónoma de San Luis Potosí, Ave. Dr. Manuel Nava #6, San Luis Potosí, SLP, 78290, México.
Iván A Aréchiga-FigueroaCONACYT-Universidad Autónoma de San Luis Potosí School of Medicine, Ave. V. Carranza 2405, San Luis Potosí, SLP, 78290, México.
Aldo A Rodríguez-MenchacaDepartment of Physiology and Biophysics, Universidad Autónoma de San Luis Potosí School of Medicine, Ave. V. Carranza 2405, San Luis Potosí, SLP, 78290, México.
Patricia Pérez-CornejoDepartment of Physiology and Biophysics, Universidad Autónoma de San Luis Potosí School of Medicine, Ave. V. Carranza 2405, San Luis Potosí, SLP, 78290, México.
H Criss HartzellDepartment of Cell Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Jorge ArreolaPhysics Institute, Universidad Autónoma de San Luis Potosí, Ave. Dr. Manuel Nava #6, San Luis Potosí, SLP, 78290, México.ORCID 0000-0002-5354-3709
Autonomous University of San Luis Potosí · MXEmory University · US

Funding

Retinal Degeneration and Chloride ChannelsR01EY014852 · NEI · EMORY UNIVERSITY · PI HARTZELL, H. CRISS · 2003 to 2020
$5.7M
Ion Channel and Lipid Scramblase Functions of Anoctamins: Roles in MyopathyR01AR067786 · NIAMS · EMORY UNIVERSITY · PI HARTZELL, H. CRISS · 2015 to 2018
$1.4M
NEI NIH HHS R01 EY014852NIAMS NIH HHS R01 AR067786
6 · The paper itself

Abstract

key pointsThe calcium-activated chloride channel TMEM16A provides a pathway for chloride ion movements that are key in preventing polyspermy, allowing fluid secretion, controlling blood pressure, and enabling gastrointestinal activity. TMEM16A is opened by voltage-dependent calcium binding and regulated by permeant anions and intracellular protons. Here we show that a low proton concentration reduces TMEM16A activity while maximum activation is obtained when the external proton concentration is high. In addition, protonation conditions determine the open probability of TMEM16A without changing its calcium sensitivity. External glutamic acid 623 (E623) is key for TMEM16A's ability to respond to external protons. At physiological pH, E623 is un-protonated and TMEM16A is activated when intracellular calcium increases; however, under acidic conditions E623 is partially protonated and works synergistically with intracellular calcium to activate the channel. These findings are critical for understanding physiological and pathological processes that involve changes in pH and chloride flux via TMEM16A. ABSTRACT: Transmembrane protein 16A (TMEM16A), also known as ANO1, the pore-forming subunit of a Ca

Indexed as

Anoctamin-1CalciumChloride ChannelsHEK293 CellsHumansModels, MolecularProtonsANO1 protein, mouseAnoctamin-1CalciumChloride ChannelsProtonscalcium sensitivitychannel regulationmutationopen probabilitypatch clampprotonsTMEM16A

Identifiers

PMID27859335
PMCPMC5330900
OpenAlexW2554919475

What OpenQuestion holds

Textmetadata
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.