Linked Life Data

12761350

Source:http://linkedlifedata.com/resource/pubmed/id/12761350

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-5-22
pubmed:abstractText
We determined the effect of flufenamic acid (FFA) and related derivatives on gap junction channel currents, applying the dual whole-cell patch-clamp technique to pairs of N2A neuroblastoma cells transfected with various connexins. FFA reduced gap junction channel currents in a reversible and concentration-dependent manner. Half-maximal concentrations for FFA-induced reduction of junctional conductance in cell pairs coupled by different connexins were similar (20 to 60 microM), indicating that FFA does not greatly discriminate between connexin subtypes. Hill coefficients for blockade were approximately 3, indicating a high degree of cooperativity. Analogs of FFA also reduced junctional conductance with similar potencies, whereas other unrelated chloride channel blockers had no effect. Inhibition of gap junction channels by FFA (pKa approximately 3.8) was increased at low external pH, suggesting that the uncharged form of the drug is important for blockade. The effect of FFA did not seem to be mediated by direct binding of the drug to the pore of the gap junction channel. Internal application of high concentrations of FFA by addition to patch pipettes did not cause inhibition of channel currents. The magnitude of inhibition was neither voltage-dependent nor influenced by the nature of permeant ion. Single-channel recordings indicated that FFA reduced the channel-open probability without modifying the current amplitude and induced slow transitions between open and closed states. We propose that FFA inhibits gap junctions by inducing a conformational change in the protein upon binding to a site that is presumably located within the membrane.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1389-97
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Closure of gap junction channels by arylaminobenzoates.
pubmed:affiliation
Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. msriniva@aecom.yu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.