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Titolo:
DISRUPTION OF THE M1 RECEPTOR GENE ABLATES MUSCARINIC RECEPTOR-DEPENDENT M-CURRENT REGULATION AND SEIZURE ACTIVITY IN MICE
Autore:
HAMILTON SE; LOOSE MD; QI M; LEVEY AI; HILLE B; MCKNIGHT GS; IDZERDA RL; NATHANSON NM;
Indirizzi:
UNIV WASHINGTON,SCH MED,DEPT PHARMACOL,BOX 357750 SEATTLE WA 98195 UNIV WASHINGTON,SCH MED,DEPT PHARMACOL SEATTLE WA 98195 OBERLIN COLL,PROGRAM NEUROSCI OBERLIN OH 44074 UNIV WASHINGTON,SCH MED,DEPT PATHOL SEATTLE WA 98195 EMORY UNIV,SCH MED,DEPT NEUROL ATLANTA GA 30322 UNIV WASHINGTON,SCH MED,DEPT PHYSIOL & BIOPHYS SEATTLE WA 98195
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 24, volume: 94, anno: 1997,
pagine: 13311 - 13316
SICI:
0027-8424(1997)94:24<13311:DOTMRG>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT SYMPATHETIC NEURONS; ACETYLCHOLINE-RECEPTOR; REPRESENTATIONAL MEMORY; CALCIUM CHANNELS; PILOCARPINE; SUBTYPES; INVOLVEMENT; EXPRESSION; IDENTIFICATION; ANTAGONISTS;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
S.E. Hamilton et al., "DISRUPTION OF THE M1 RECEPTOR GENE ABLATES MUSCARINIC RECEPTOR-DEPENDENT M-CURRENT REGULATION AND SEIZURE ACTIVITY IN MICE", Proceedings of the National Academy of Sciences of the United Statesof America, 94(24), 1997, pp. 13311-13316

Abstract

Muscarinic acetylcholine receptors are members of the G protein-coupled receptor superfamily expressed in neurons, cardiomyocytes, smooth muscle, and a variety of epithelia. Five subtypes of muscarinic acetylcholine receptors have been discovered by molecular cloning, but their pharmacological similarities and frequent colocalization make it difficult to assign functional roles for individual subtypes in specific neuronal responses. We have used gene targeting by homologous recombination in embryonic stem cells to produce mice lacking the mi receptor. These mice show no obvious behavioral or histological defects, and the m2, m3, and m4 receptors continue to be expressed in brain with no evidence of compensatory induction. However, the robust suppression of the M-current potassium channel activity evoked by muscarinic agonists in sympathetic ganglion neurons is completely lost in mi mutant mice. In addition, both homozygous and heterozygous mutant mice are highly resistant to the seizures produced by systemic administration of the muscarinic agonist pilocarpine. Thus, the mi receptor subtype mediates M current modulation in sympathetic neurons and induction of seizure activity in the pilocarpine model of epilepsy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/11/20 alle ore 21:34:45