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Titolo:
Positive allosteric modulators of AMPA receptors reduce proton-induced receptor desensitization in rat hippocampal neurons
Autore:
Lei, SB; Orser, BA; Thatcher, GRL; Reynolds, JN; MacDonald, JF;
Indirizzi:
Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 ysiol, Toronto, ON M5S 1A8, Canada Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 macol, Toronto, ON M5S 1A8, Canada Univ Toronto, Dept Anaesthesia, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 hesia, Toronto, ON M5S 1A8, Canada Queens Univ, Dept Pharmacol & Toxicol, Kingston, ON K7L 3N6, Canada QueensUniv Kingston ON Canada K7L 3N6 icol, Kingston, ON K7L 3N6, Canada
Titolo Testata:
JOURNAL OF NEUROPHYSIOLOGY
fascicolo: 5, volume: 85, anno: 2001,
pagine: 2030 - 2038
SICI:
0022-3077(200105)85:5<2030:PAMOAR>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIGAND-BINDING DOMAIN; D-ASPARTATE RECEPTOR; GLUTAMATE-RECEPTOR; KAINATE RECEPTORS; NMDA RECEPTORS; SYNAPTIC TRANSMISSION; CYCLOTHIAZIDE; ACTIVATION; INHIBITION; POLYAMINES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Lei, SB Univ Toronto, Dept Physiol, Med Sci Bldg, Toronto, ON M5S 1A8, Canada Univ Toronto Med Sci Bldg Toronto ON Canada M5S 1A8 5S 1A8, Canada
Citazione:
S.B. Lei et al., "Positive allosteric modulators of AMPA receptors reduce proton-induced receptor desensitization in rat hippocampal neurons", J NEUROPHYS, 85(5), 2001, pp. 2030-2038

Abstract

Whole-cell or outside-out patch recordings were used to investigate the effects of protons and positive modulators of alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on the desensitization of glutamate-evoked AMPA receptor currents in isolated hippocampal CA1 neurons. Protons inhibited glutamate-evoked currents (IC50 of 6.2 pH units) but also enhanced the apparent rate and extent of AMPA receptor desensitization. The proton-induced enhancement of desensitization could not be attributed to a reduction in the rate of recovery from desensitization or to a change in thekinetics of deactivation. Non-stationary variance analysis indicated that protons reduced maximum open probability without changing the conductance of AMPA channels. The positive modulators of AMPA receptor desensitization, cyclothiazide and GT-21-005 (an organic nitrate), reduced the proton sensitivity of AMPA receptor desensitization, which suggests that they interact with protons to diminish desensitization. In contrast, the effects of wheat germ agglutinin and aniracetam on AMPA receptor desensitization were independent of pH. These results demonstrate that a reduction in the proton sensitivity of receptor desensitization contributes to the mechanism of action of some positive modulators of AMPA receptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 13:04:35