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Study implicates potassium channel mutations in neurodegeneration and mental retardation

For the first time, researchers have linked mutations in a gene that regulates how potassium enters cells to a neurodegenerative disease and to another disorder that causes mental retardation and coordination problems. The findings may lead to new ways of treating a broad range of disorders, including Alzheimer's and Parkinson's diseases. The study was funded in part by the National Institutes of Health's National Institute of Neurological Disorders and Stroke (NINDS).

"This type of gene has never before been linked to nerve cell death," says Stefan Pulst, M.D., of Cedars-Sinai Medical Center at the University of California, Los Angeles, who led the new study. The report will appear in the February 26, 2006, advance online publication of Nature Genetics.*

In the study, the researchers looked for the gene that caused a neurodegenerative movement disorder called spinocerebellar ataxia in a Filipino family. This disorder typically appears in adulthood and causes loss of neurons in the brain's cerebellum, resulting in progressive loss of coordination (ataxia). Dr. Pulst and his colleagues traced the disease in this family to mutations in a gene called KCNC3. The gene codes for one of the proteins that form potassium channels pore-like openings in the cell membrane that control the flow of potassium ions into the cell. The researchers found a different KCNC3 mutation in a previously identified French family with a disease called spinocerebellar ataxia type 13, which causes childhood-onset ataxia, cerebellar degeneration, and mild mental retardation.

The KCNC3 gene codes for a type of potassium channel that normally opens and closes very quickly. This type of channel is particularly important in "fast-bursting neurons" that fire hundreds of times per second in the brain. "Fast-bursting neurons are like building blocks they are used in the nervous system a lot," Dr. Pulst says. Among other places, these neurons are found in the brain's
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Contact: Natalie Frazin or Paul Girolami
301-496-5924
NIH/National Institute of Neurological Disorders and Stroke
26-Feb-2006


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