Altered responses to potassium in cerebellar neurons from weaver heterozygote mice

A. P. Fox, S. Dlouhy, B. Ghetti, J. H. Hurley, P. G.P. Nucifora, D. J. Nelson, L. Won, A. Heller

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The pleiotropic weaver disease is caused by the mutation of a single amino acid in the G-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 K+-channel function or intracellular Ca2+ concentrations ([Ca2+](i)) play a role in the augmented cell loss observed in wv/+ 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.

Original languageEnglish (US)
Pages (from-to)298-306
Number of pages9
JournalExperimental Brain Research
Volume123
Issue number3
DOIs
StatePublished - Nov 30 1998

Keywords

  • Calcium
  • Cerebellar granule cells
  • GIRK2
  • Heterozygote
  • Weaver mice

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Altered responses to potassium in cerebellar neurons from weaver heterozygote mice'. Together they form a unique fingerprint.

  • Cite this