Evidence map›Paper›PMID 27413167›Full record

ArticleAmerican journal of physiology. Cell physiology2016

Influence of intracellular Ca2+ and alternative splicing on the pharmacological profile of ANO1 channels.

Tae Sik Sung, Kate O'Driscoll, Haifeng Zheng, Nicholas J Yapp, Normand Leblanc, Sang Don Koh, Kenton M Sanders

Open access · hybridAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

23 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Review
  3. The CaActa pharmaceutica Sinica. B · 2021
    Review
  4. Allosteric modulation of alternatively spliced CaProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  5. Article
  6. Review
  7. NaFrontiers in physiology · 2020
    Article
  8. Molecular mechanism of TMEM16A regulation: role of CaMKII and PP1/PP2A.American journal of physiology. Cell physiology · 2019
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Functional comparison of anoctamin 1 antagonists on human uterine smooth muscle contractility and excitability.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2018
    Article
  19. Article
  20. 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

7 authors at 1 institution in 1 country.

Tae Sik SungDepartment of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada; and.
Kate O'DriscollDepartment of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada; and.
Haifeng ZhengDepartment of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada; and.
Nicholas J YappDepartment of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada; and.
Normand LeblancDepartment of Pharmacology, Center for Cardiovascular Research, University of Nevada School of Medicine, Reno, Nevada.
Sang Don KohDepartment of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada; and.
Kenton M SandersDepartment of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada; and ksanders@medicine.nevada.edu.
University of Nevada, Reno · US

Funding

Tissue, Cell and Tissue Culture CoreP01DK041315 · NIDDK · UNIVERSITY OF NEVADA RENO · PI WARD, SEAN M · 1989 to 2018
$26.3M
Single Cell Molecular ExpressionP30GM110767 · NIGMS · UNIVERSITY OF NEVADA RENO · PI YAN, WEI · 2014 to 2018
$5.4M
NIDDK NIH HHS P01 DK041315NIGMS NIH HHS P30 GM110767
6 · The paper itself

Abstract

Anoctamin-1 (ANO1) is a Ca(2+)-activated Cl(-) channel expressed in many types of cells. Splice variants of ANO1 have been shown to influence the biophysical properties of conductance. It has been suggested that several new antagonists of ANO1 with relatively high affinity and selectivity might be useful for experimental and, potentially, therapeutic purposes. We investigated the effects of intracellular Ca(2+) concentration ([Ca(2+)]i) at 100-1,000 nM, a concentration range that might be achieved in cells during physiological activation of ANO1 channels, on blockade of ANO1 channels expressed in HEK-293 cells. Whole cell and excised patch configurations of the patch-clamp technique were used to perform tests on a variety of naturally occurring splice variants of ANO1. Blockade of ANO1 currents with aminophenylthiazole (T16Ainh-A01) was highly dependent on [Ca(2+)]i Increasing [Ca(2+)]i reduced the potency of this blocker. Similar Ca(2+)-dependent effects were also observed with benzbromarone. Experiments on excised, inside-out patches showed that the diminished potency of the blockers caused by intracellular Ca(2+) might involve a competitive interaction for a common binding site or repulsion of the blocking drugs by electrostatic forces at the cytoplasmic surface of the channels. The degree of interaction between the channel blockers and [Ca(2+)]i depends on the splice variant expressed. These experiments demonstrate that the efficacy of ANO1 antagonists depends on [Ca(2+)]i, suggesting a need for caution when ANO1 blockers are used to determine the role of ANO1 in physiological functions and in their use as therapeutic agents.

Indexed as

Alternative SplicingAnimalsAnoctamin-1BenzbromaroneCalciumCell LineChloride ChannelsCytoplasmHEK293 CellsHumansMicePatch-Clamp TechniquesPyrimidinesThiazolesANO1 protein, mouseAnoctamin-1BenzbromaroneCalciumChloride ChannelsPyrimidinesT16AInh-A01Thiazolesanion channelCa2+-activated Cl− channelsCl− channel blockerion channel

Identifiers

PMID27413167
PMCPMC5129757
OpenAlexW2465963454

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.