Linked Life Data

9495819

Source:http://linkedlifedata.com/resource/pubmed/id/9495819

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-3-27
pubmed:abstractText
All members of the receptor-operated ion channel family that includes gamma-aminobutyric acid (GABA), glycine, nicotinic acetylcholine, and serotonin type 3 receptors have a conserved leucine near the center of the presumed second membrane-spanning domain. This leucine has been postulated to play a role in the gating of the pore. In this study, we examined the effects of mutating this leucine (L301) on the function of human homomeric rho1 GABA receptors. Oocytes expressing rho1 GABA receptors in which this leucine was substituted with alanine (A), glycine (G), serine (S), threonine (T), valine, or tyrosine, but not isoleucine or phenylalanine, demonstrated larger-than-normal resting conductances in the absence of GABA. This resting conductance had a reversal potential (and shifted reversal potential with chloride substitution) indistinguishable from that of the wild-type rho1 GABA-activated current. This resting conductance was antagonized by picrotoxin and, in the case of the A, G, S, and T substitutions, by GABA itself. Although the rho1 competitive antagonist 3-aminopropyl(methyl)-phosphinic acid did not block the resting conductance, this compound did competitively inhibit the GABA-mediated antagonism of the resting conductance. At higher concentrations, both 3-aminopropyl(methyl)-phosphinic acid and GABA directly activated the A, G, S, and T mutant receptors. Taken together, these data suggest that substitution of this highly conserved leucine with either small or polar residues produced rho1 GABA receptors that can open in the absence of GABA and support the hypothesis that this leucine may play a key role in the gating of the pore.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
511-23
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Substitutions of the highly conserved M2 leucine create spontaneously opening rho1 gamma-aminobutyric acid receptors.
pubmed:affiliation
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't