Abstract
In the neurological mutant mouse weaver, granule cell precursors proliferate normally in the external germinal layer of the cerebellar cortex, but fail to differentiate. Granule neurons purified from weaver cerebella have greatly reduced G protein-activated inwardly rectifying K+ currents; instead, they display a constitutive Na+ conductance. Expression of the weaver GIRK2 channel in oocytes confirms that the mutation leads to constitutive activation, loss of monovalent cation selectivity, and increased sensitivity to three channel blockers. Pharmacological blockade of the Na+ influx in weaver granule cells restores their ability to differentiate normally. Thus, Na+ flux through the weaver GIRK2 channel underlies the failure of granule cell development in situ.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Cell Differentiation
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Cerebellar Cortex / physiology*
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DNA Primers
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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Gene Expression Regulation, Developmental
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Guanosine Triphosphate / physiology
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In Situ Hybridization
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Mice
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Mice, Neurologic Mutants
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Molecular Sequence Data
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Oocytes
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Point Mutation
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Potassium / physiology
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Potassium Channels / genetics*
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Potassium Channels / physiology*
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Potassium Channels, Inwardly Rectifying*
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Receptors, Muscarinic / physiology
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Signal Transduction
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Sodium / physiology
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Transfection
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Xenopus laevis
Substances
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DNA Primers
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Receptors, Muscarinic
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Guanosine Triphosphate
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Sodium
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Potassium
Associated data
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GENBANK/L35771
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GENBANK/U11859
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GENBANK/U11860