Evidence map›Paper›PMID 8744307›Full record

ArticleBiophysical journal1996

Tolbutamide causes open channel blockade of cystic fibrosis transmembrane conductance regulator Cl- channels.

C J Venglarik, B D Schultz, A D DeRoos, A K Singh, R J Bridges

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biophysical journal, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

19 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
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  3. Review
  4. Murine and human CFTR exhibit different sensitivities to CFTR potentiators.American journal of physiology. Lung cellular and molecular physiology · 2015
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  12. Functional coupling between sulfonylurea receptor type 1 and a nonselective cation channel in reactive astrocytes from adult rat brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2003
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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 1 institution in 1 country.

C J VenglarikDepartment of Physiology and Biophysics, University of Alabama at Birmingham 35294, USA.
B D Schultz
A D DeRoos
A K Singh
R J Bridges
University of Alabama at Birmingham · US

Funding

CFTR SINGLE CHANNEL RECONSTITUTION STUDIESR01DK045970 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BRIDGES, ROBERT J. · 1992 to 1996
–
NIDDK NIH HHS DK-45970
6 · The paper itself

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial Cl- channel that is regulated by protein kinase A and cytosolic nucleotides. Previously, Sheppard and Welsh reported that the sulfonylureas glibenclamide and tolbutamide reduced CFTR whole cell currents. The aim of this study was to quantify the effects of tolbutamide on CFTR gating in excised membrane patches containing multiple channels. We chose tolbutamide because weak (i.e., fast-type) open channel blockers introduce brief events into multichannel recordings that can be readily quantified by current fluctuation analysis. Inspection of current records revealed that the addition of tolbutamide reduced the apparent single-channel current amplitude and increased the open-channel noise, as expected for a fast-type open channel blocker. The apparent decrease in unitary current amplitude provides a measure of open probability within a burst (P0 Burst), and the resulting concentration-response relationship was described by a simple Michaelis-Menten inhibition function. The concentration of tolbutamide causing a 50% reduction of Po Burst (540 +/- 20 microM) was similar to the concentration producing a 50% inhibition of short-circuit current across T84 colonic epithelial cell monolayers (400 +/- 20 microM). Changes in CFTR gating were then quantified by analyzing current fluctuations. Tolbutamide caused a high-frequency Lorentzian (corner frequency, fc > 300 Hz) to appear in the power density spectrum. The fc of this Lorentzian component increased as a linear function of tolbutamide concentration, as expected for a pseudo-first-order open-blocked mechanism and yielded estimates of the on rate (koff = 2.8 +/- 0.3 microM-1 s-1), the off rate (kon = 1210 +/- 225 s-1), and the dissociation constant (KD = 430 +/- 80 microM). Based on these observations, we propose that there is a bimolecular interaction between tolbutamide and CFTR, causing open channel blockade.

Indexed as

Biophysical PhenomenaBiophysicsCell LineCyclic AMPCystic Fibrosis Transmembrane Conductance RegulatorHumansIon Channel GatingKineticsPatch-Clamp TechniquesTolbutamideCFTR protein, humanCyclic AMPCystic Fibrosis Transmembrane Conductance RegulatorTolbutamide

Identifiers

PMID8744307
PMCPMC1225249
OpenAlexW2009378796

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.