Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Mutation of the 9 ' leucine in the GABA(A) receptor gamma 2L subunit produces an apparent decrease in desensitization by stabilizing open states without altering desensitized states
Autore:
Bianchi, MT; Macdonald, RL;
Indirizzi:
Vanderbilt Univ, Dept Neurol, Nashville, TN 37212 USA Vanderbilt Univ Nashville TN USA 37212 pt Neurol, Nashville, TN 37212 USA Univ Michigan, Grad Program Neurosci, Ann Arbor, MI 48104 USA Univ Michigan Ann Arbor MI USA 48104 am Neurosci, Ann Arbor, MI 48104 USA Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA Vanderbilt Univ Nashville TN USA 37212 & Biophys, Nashville, TN 37212 USA Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37212 USA Vanderbilt Univ Nashville TN USA 37212 Pharmacol, Nashville, TN 37212 USA
Titolo Testata:
NEUROPHARMACOLOGY
fascicolo: 6, volume: 41, anno: 2001,
pagine: 737 - 744
SICI:
0028-3908(200111)41:6<737:MOT9'L>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACETYLCHOLINE-RECEPTOR; M2 DOMAIN; EXPRESSION;
Keywords:
GABA(A) receptor; gating; desensitization; concentration-jump; excised patch; simulation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Macdonald, RL Vanderbilt Univ, Dept Neurol, 2100 Pierce Ave, Nashville, TN37212 USA Vanderbilt Univ 2100 Pierce Ave Nashville TN USA 37212 2 USA
Citazione:
M.T. Bianchi e R.L. Macdonald, "Mutation of the 9 ' leucine in the GABA(A) receptor gamma 2L subunit produces an apparent decrease in desensitization by stabilizing open states without altering desensitized states", NEUROPHARM, 41(6), 2001, pp. 737-744

Abstract

A conserved leucine near the middle (9' position) of the second transmembrane domain of ligand-gated ion channels has been implicated in both gating and desensitization. Specifically, L9'S and L9'T mutations decreased agonist EC50, decreased apparent desensitization and prolonged deactivation in members of the LGIC superfamily, suggesting that this residue may regulate channel properties including desensitization. GABA(A) receptors desensitize in three phases, but in previous 9' leucine studies. only slow phases of desensitization were resolved. We used excised patches containing alpha1 beta3gamma 2L or alpha1 beta3 gamma 2L(L9'S) GABA(A) receptors and combined single channel recording and concentration jump techniques to reevaluate the effects of this mutation on desensitization. Although desensitization extentwas decreased in mutated channels., desensitization still occurred in three phases, suggesting that desensitized states may be intact. Interestingly,deactivation rate was slowed by the mutation, opposite to that expected ifdesensitization was attenuated. alpha1 beta3 gamma 2L(L9'S) receptor single channels had increased open durations. Simulations revealed that stabilizing the open state (by decreasing the channel closing rate) could account for multiple macroscopic findings: left-shifted GABA EC50 smaller extent of desensitization. slower desensitization rate, and longer deactivation. We concluded that changes in efficacy can alter macroscopic desensitization without affecting desensitized states per se. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 10:36:44