Abstract
1. Changes in intracellular Ca2+ ([Ca2+]i) levels provide signals that allow neurons to respond to a host of external stimuli. A major mechanism for elevating Ca2+ ([Ca2+]i) is the influx of extracellular Ca2+ through voltage-gated channels (CaV) in the plasma membrane. in CaV due to mutations in genes encoding channel proteins are increasingly being implicated in causing disease conditions, termed channelopathies.
2. Seven spontaneous mutations with cerebellar ataxia and generalized absence epilepsy have been identified in mice (tottering, leaner, rolling Nagoya, rocker, lethargic, ducky, and stargazer), and these overlapping phenotypes are directly related to mutations in genes encoding the four separate subunits that together form the multimeric neuronal CaV complex.
3. The discovery and systematic analysis of these animal models is helping to clarify how different mutations affect channel function and how altered channel function produces disease.
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Felix, R. Insights from Mouse Models of Absence Epilepsy into Ca2+ Channel Physiology and Disease Etiology. Cell Mol Neurobiol 22, 103–120 (2002). https://doi.org/10.1023/A:1019807719343
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DOI: https://doi.org/10.1023/A:1019807719343