Evidence of elevated intracellular calcium levels in weaver homozygote mice

A. B. Harkins, Stephen Dlouhy, Bernardino Ghetti, A. L. Cahill, L. Won, B. Heller, A. Heller, A. P. Fox

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

1. A mutation in the G-protein-linked, inwardly rectifying K+ channel GIRK2 leads to the loss of cerebellar and dopaminergic mesencephalic neurons in weaver mice. The steps leading to cell death are not well understood but may involve constitutive influx of Na+ and Ca2+ into the neurons. 2. We found that resting [Ca2+](i) was dramatically higher in cerebellar neurons from weaver mice compared to wild-type neurons. 3. High-K+ stimuli elicited much smaller changes in [Ca2+](i) in weaver cerebellar neurons compared to wild-type neurons. 4. weaver cerebellar granule cells could be rescued from cell death by the GIRK2wv cationic channel blocker, QX-314. 5. QX-314 lowered resting intracellular Ca2+ levels in weaver cerebellar granule cells. 6. These results suggest that changes in resting [Ca2+](i) levels and alterations in K+ channel function are most likely to contribute to the developmental abnormalities and increased cerebellar cell death observed in weaver mice.

Original languageEnglish
Pages (from-to)447-455
Number of pages9
JournalJournal of Physiology
Volume524
Issue number2
StatePublished - Apr 15 2000

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Neurologic Mutant Mice
Homozygote
Calcium
Neurons
Cell Death
Inwardly Rectifying Potassium Channel
Dopaminergic Neurons
GTP-Binding Proteins
Mutation

ASJC Scopus subject areas

  • Physiology

Cite this

Harkins, A. B., Dlouhy, S., Ghetti, B., Cahill, A. L., Won, L., Heller, B., ... Fox, A. P. (2000). Evidence of elevated intracellular calcium levels in weaver homozygote mice. Journal of Physiology, 524(2), 447-455.

Evidence of elevated intracellular calcium levels in weaver homozygote mice. / Harkins, A. B.; Dlouhy, Stephen; Ghetti, Bernardino; Cahill, A. L.; Won, L.; Heller, B.; Heller, A.; Fox, A. P.

In: Journal of Physiology, Vol. 524, No. 2, 15.04.2000, p. 447-455.

Research output: Contribution to journalArticle

Harkins, AB, Dlouhy, S, Ghetti, B, Cahill, AL, Won, L, Heller, B, Heller, A & Fox, AP 2000, 'Evidence of elevated intracellular calcium levels in weaver homozygote mice', Journal of Physiology, vol. 524, no. 2, pp. 447-455.
Harkins, A. B. ; Dlouhy, Stephen ; Ghetti, Bernardino ; Cahill, A. L. ; Won, L. ; Heller, B. ; Heller, A. ; Fox, A. P. / Evidence of elevated intracellular calcium levels in weaver homozygote mice. In: Journal of Physiology. 2000 ; Vol. 524, No. 2. pp. 447-455.
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