Evidence map›Paper›PMID 19054772›Full record

ArticleThe Journal of biological chemistry2009

Membrane hyperpolarization drives cation influx and fungicidal activity of amiodarone.

Lydie Maresova, Sabina Muend, Yong-Qiang Zhang, Hana Sychrova, Rajini Rao

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

32 citing papers in PubMed, 77 citations in OpenAlex.

  1. Anandamide Targets Membrane Integrity in Non-Journal of fungi (Basel, Switzerland) · 2026
    Article
  2. Trk1 potassium transport is crucial for effectiveProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
  4. Exit, O Sodium!Function (Oxford, England) · 2024
    Article
  5. Calcium Ion Channels inJournal of fungi (Basel, Switzerland) · 2023
    Review
  6. Article
  7. Aequorin as a Useful Calcium-Sensing Reporter inJournal of fungi (Basel, Switzerland) · 2021
    Article
  8. Review
  9. Frontiers in microbiology · 2020
    Article
  10. Plasma Membrane Potential ofMicroorganisms · 2019
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. An integrative model of ion regulation in yeast.PLoS computational biology · 2013
    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

5 authors at 3 institutions in 2 countries.

Lydie MaresovaDepartment of Membrane Transport, Institute of Physiology, Academy of Sciences CR, Prague, Czech Republic.
Sabina MuendDepartment of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Yong-Qiang ZhangDepartment of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Hana SychrovaDepartment of Membrane Transport, Institute of Physiology, Academy of Sciences CR, Prague, Czech Republic.
Rajini RaoDepartment of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205. Electronic address: rrao@jhmi.edu.
Czech Academy of Sciences, Institute of Physiology · CZJohns Hopkins University · USJohns Hopkins Medicine · US

Funding

Cellular Basis for the Antifungal Activity of AmiodaroneR01AI065983 · NIAID · JOHNS HOPKINS UNIVERSITY · PI RAO, RAJINI · 2006 to 2010
$2.1M
NIAID NIH HHS R01 AI 065983
6 · The paper itself

Abstract

Cationic amphipathic drugs, such as amiodarone, interact preferentially with lipid membranes to exert their biological effect. In the yeast Saccharomyces cerevisiae, toxic levels of amiodarone trigger a rapid influx of Ca(2+) that can overwhelm cellular homeostasis and lead to cell death. To better understand the mechanistic basis of antifungal activity, we assessed the effect of the drug on membrane potential. We show that low concentrations of amiodarone (0.1-2 microm) elicit an immediate, dose-dependent hyperpolarization of the membrane. At higher doses (>3 microm), hyperpolarization is transient and is followed by depolarization, coincident with influx of Ca(2+) and H(+) and loss in cell viability. Proton and alkali metal cation transporters play reciprocal roles in membrane polarization, depending on the availability of glucose. Diminishment of membrane potential by glucose removal or addition of salts or in pma1, tok1Delta, ena1-4Delta, or nha1Delta mutants protected against drug toxicity, suggesting that initial hyperpolarization was important in the mechanism of antifungal activity. Furthermore, we show that the link between membrane hyperpolarization and drug toxicity is pH-dependent. We propose the existence of pH- and hyperpolarization-activated Ca(2+) channels in yeast, similar to those described in plant root hair and pollen tubes that are critical for cell elongation and growth. Our findings illustrate how membrane-active compounds can be effective microbicidals and may pave the way to developing membrane-selective agents.

Indexed as

Membrane ProteinsAmiodaroneFluorescenceHumansImmunoprecipitationIon TransportSaccharomyces cerevisiaeAmiodaroneMembrane Proteins

Identifiers

PMID19054772
PMCPMC2631971
OpenAlexW1969189307

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.