Linked Life Data

20371809

Source:http://linkedlifedata.com/resource/pubmed/id/20371809

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2010-4-7
pubmed:abstractText
GABA(A) receptors (GABA(A)Rs) regulate the majority of fast inhibition in the mammalian brain and are the target for multiple drug types, including sleep aids, anti-anxiety medication, anesthetics, alcohol, and neurosteroids. A variety of subunits, including the highly distributed gamma2, allow for pharmacologic and kinetic differences in particular brain regions. The two common splice variants gamma2S (short) and gamma2L (long) show different patterns of regional distribution both in adult brain and during the course of development, but show few notable differences when incorporated into pentameric receptors. However, results presented here show that the gamma2S variant can strongly affect both GABA(A)R pharmacology and kinetics by acting as an external modulator of fully formed receptors. Mutation of one serine residue can confer gamma2S-like properties to gamma2L subunits, and addition of a modified gamma2 N-terminal polypeptide to the cell surface recapitulates the pharmacological effect. Thus, rather than incorporation of a separate accessory protein as with voltage-gated channels, this is an example of an ion channel using a common subunit for dual purposes. The modified receptor properties conferred by accessory gamma2S have implications for understanding GABA(A)R pharmacology, receptor kinetics, stoichiometry, GABAergic signaling in the brain during development, and altered function in disease states such as epilepsy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4895-903
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The short splice variant of the gamma 2 subunit acts as an external modulator of GABA(A) receptor function.
pubmed:affiliation
Department of Physiology, Ponce School of Medicine, Ponce, Puerto Rico 00732. drew.boileau@gmail.com
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural