title: Evidence of elevated intracellular calcium levels in weaver homozygote mice.
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.
authors.affiliation: Department of Neurobiology, Pharmacology and Physiology, University of Chicago, 947 E. 58th Street, Chicago, IL 60637, USA. amy@drugs.bsd.uchicago.edu
authors.forename: A B
authors.initials: AB
authors.lastname: Harkins
authors.forename: S
authors.initials: S
authors.lastname: Dlouhy
authors.forename: B
authors.initials: B
authors.lastname: Ghetti
authors.forename: A L
authors.initials: AL
authors.lastname: Cahill
authors.forename: L
authors.initials: L
authors.lastname: Won
authors.forename: B
authors.initials: B
authors.lastname: Heller
authors.forename: A
authors.initials: A
authors.lastname: Heller
authors.forename: A P
authors.initials: AP
authors.lastname: Fox
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D006720:Homozygote; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008818:Mice, Neurologic Mutants; D009474:Neurons / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D013268:Stimulation, Chemical
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C012647:QX-314; D008012:Lidocaine; D011188:Potassium; D002118:Calcium