Evidence map›Paper›PMID 28076814›Full record

ArticleBiophysical journal2017

GsMTx4: Mechanism of Inhibiting Mechanosensitive Ion Channels.

Radhakrishnan Gnanasambandam, Chiranjib Ghatak, Anthony Yasmann, Kazuhisa Nishizawa, Frederick Sachs, Alexey S Ladokhin, Sergei I Sukharev, Thomas M Suchyna

Open access · bronzeAbstract read
In one paragraph

Article in Biophysical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers.

0numbers the graph read from it
0cells of the map it votes in
162citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

162 citing papers in PubMed, 240 citations in OpenAlex.

  1. Review
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  9. Article
  10. Amoeboid cancer cells at a glance.Journal of cell science · 2026
    Review
  11. Article
  12. Mechanosensitive Piezo1 Channels in Enamel Cells.Calcified tissue international · 2026
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Mechano-electrical feedback in transgenic rabbit models of long QT syndrome Type 2 and short QT syndrome Type 1.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026
    Article
  18. Article
  19. Review
  20. PIEZO1 in Immune Cells: From Force to Function.Results and problems in cell differentiation · 2026
    Review

102 more citing papers are in PubMed but not listed here.

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

8 authors at 4 institutions in 2 countries.

Radhakrishnan GnanasambandamDepartment of Physiology and Biophysics, State University of New York, Buffalo, New York.
Chiranjib GhatakDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas.
Anthony YasmannDepartment of Biology, University of Maryland, College Park, Maryland.
Kazuhisa NishizawaClinical Laboratory Science, Teikyo University School of Medical Technology, Tokyo, Japan.
Frederick SachsDepartment of Physiology and Biophysics, State University of New York, Buffalo, New York.
Alexey S LadokhinDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas.
Sergei I SukharevDepartment of Biology, University of Maryland, College Park, Maryland.
Thomas M SuchynaDepartment of Physiology and Biophysics, State University of New York, Buffalo, New York. Electronic address: suchyna@buffalo.edu.
University at Buffalo, State University of New York · USUniversity of Kansas Medical Center · USUniversity of Maryland, College Park · USTeikyo University · JP

Funding

Mechanosensitive ion channels and cortical mechanicsR01HL054887 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI SACHS, FREDERICK · 1995 to 2016
$9.6M
pH-Triggered Membrane Insertion of ProteinsR01GM069783 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI COCCO, MELANIE J, KURNIKOVA, MARIA G · 2004 to 2014
$2.5M
The bacterial mechanosentitive channel as a multimodal sensor deviceR01GM107652 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI ANISHKIN, ANDRIY, SINTIM, HERMAN O · 2013 to 2016
$1.1M
NHLBI NIH HHS R01 HL054887NIGMS NIH HHS R01 GM069783NIGMS NIH HHS R01 GM107652
6 · The paper itself

Abstract

GsMTx4 is a spider venom peptide that inhibits cationic mechanosensitive channels (MSCs). It has six lysine residues that have been proposed to affect membrane binding. We synthesized six analogs with single lysine-to-glutamate substitutions and tested them against Piezo1 channels in outside-out patches and independently measured lipid binding. Four analogs had ∼20% lower efficacy than the wild-type (WT) peptide. The equilibrium constants calculated from the rates of inhibition and washout did not correlate with the changes in inhibition. The lipid association strength of the WT GsMTx4 and the analogs was determined by tryptophan autofluorescence quenching and isothermal calorimetry with membrane vesicles and showed no significant differences in binding energy. Tryptophan fluorescence-quenching assays showed that both WT and analog peptides bound superficially near the lipid-water interface, although analogs penetrated deeper. Peptide-lipid association, as a function of lipid surface pressure, was investigated in Langmuir monolayers. The peptides occupied a large fraction of the expanded monolayer area, but that fraction was reduced by peptide expulsion as the pressure approached the monolayer-bilayer equivalence pressure. Analogs with compromised efficacy had pressure-area isotherms with steeper slopes in this region, suggesting tighter peptide association. The pressure-dependent redistribution of peptide between "deep" and "shallow" binding modes was supported by molecular dynamics (MD) simulations of the peptide-monolayer system under different area constraints. These data suggest a model placing GsMTx4 at the membrane surface, where it is stabilized by the lysines, and occupying a small fraction of the surface area in unstressed membranes. When applied tension reduces lateral pressure in the lipids, the peptides penetrate deeper acting as "area reservoirs" leading to partial relaxation of the outer monolayer, thereby reducing the effective magnitude of stimulus acting on the MSC gate.

Indexed as

Mechanical PhenomenaBiomechanical PhenomenaHEK293 CellsHumansIntercellular Signaling Peptides and ProteinsIon Channel GatingIon ChannelsLipid BilayersPeptidesPressureSpider VenomsStress, MechanicalIntercellular Signaling Peptides and ProteinsIon ChannelsLipid BilayersMTx4 protein, Grammostola spatulataPeptidesSpider Venoms

Identifiers

PMID28076814
PMCPMC5231890
OpenAlexW2568618669

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.