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Titolo:
ALTERED RESPONSES TO POTASSIUM IN CEREBELLAR NEURONS FROM WEAVER HETEROZYGOTE MICE
Autore:
FOX AP; DLOUHY S; GHETTI B; HURLEY JH; NUCIFORA PGP; NELSON DJ; WON L; HELLER A;
Indirizzi:
UNIV CHICAGO,DEPT PHARMACOL & PHYSIOL SCI,947 E 58TH ST CHICAGO IL 60637 INDIANA UNIV,SCH MED,DEPT MED & MOL GENET INDIANAPOLIS IN 46202 INDIANA UNIV,SCH MED,DEPT PATHOL & LAB MED INDIANAPOLIS IN 46202
Titolo Testata:
Experimental Brain Research
fascicolo: 3, volume: 123, anno: 1998,
pagine: 298 - 306
SICI:
0014-4819(1998)123:3<298:ARTPIC>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECTIFIER K+ CHANNEL; DORSAL RAPHE NEURONS; BETA-GAMMA-SUBUNITS; PERMEANT CA2+ CHELATORS; G-PROTEIN; INWARD RECTIFIER; GRANULE CELLS; MUTANT MICE; DOPAMINE DEFICIENCY; PURKINJE-CELLS;
Keywords:
WEAVER MICE; HETEROZYGOTE; CEREBELLAR GRANULE CELLS; CALCIUM; GIRK2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
A.P. Fox et al., "ALTERED RESPONSES TO POTASSIUM IN CEREBELLAR NEURONS FROM WEAVER HETEROZYGOTE MICE", Experimental Brain Research, 123(3), 1998, pp. 298-306

Abstract

The pleiotropic weaver disease is caused by the mutation of a single amino acid in the C-protein-linked inwardly rectifying K+ channel, GIRK2. In homozygous (wv/wv) animals, the disease is characterized by loss of cerebellar and dopaminergic mesencephalic neurons as well as testicular cells, which produce ataxia, fine tremors, and sterility, respectively. Heterozygous (wv/+) animals show no obvious motor impairments, although some loss of both cerebellar and dopaminergic neurons is observed and wv/+ males become sterile at 3.5 months of age. Abnormal influxes of Na+ and Ca2+ have been linked to cerebellar cell death in wv/wv animals, but it's not clear whether similar changes are observed in wv/+ animals. To discover whether changes in Kf-channel function or intracellular Ca2+ concentrations ([Ca2+](i)) play a role in the augmented cell loss observed in mv/+ animals when compared with +/+ animals, we studied cultured cerebellar granule cells prepared from either wv/+ or +/+ animals. Resting [Ca2+](i) was elevated in wv/+ relative to /+ animals. Further, depolarizations of cells with elevated K+ solutions elicited much smaller changes in [Ca2+](i) in wv/+ animals than in+/+ animals, presumably due to altered GIRK2 channel function. Both wv/+ and +/+ cells showed similar changes in [Ca2+](i) when cells were depolarized by glutamate (1 mM), suggesting that both glutamate receptors and Ca2+ channels were unchanged in wv/+ animals. In summary, our results suggest that wv/+ cerebellar granule cells exhibit elevated resting [Ca2+](i) levels and altered K+-channel function, which may contribute to the developmental abnormalities and increased cell death observed.

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Documento generato il 27/11/20 alle ore 11:50:34