Abstract
In the mammalian central nervous system, slow synaptic excitation involves the activation of metabotropic glutamate receptors (mGluRs). It has been proposed that C1-type transient receptor potential (TRPC1) channels underlie this synaptic excitation, but our analysis of TRPC1-deficient mice does not support this hypothesis. Here, we show unambiguously that it is TRPC3 that is needed for mGluR-dependent synaptic signaling in mouse cerebellar Purkinje cells. TRPC3 is the most abundantly expressed TRPC subunit in Purkinje cells. In mutant mice lacking TRPC3, both slow synaptic potentials and mGluR-mediated inward currents are completely absent, while the synaptically mediated Ca2+ release signals from intracellular stores are unchanged. Importantly, TRPC3 knockout mice exhibit an impaired walking behavior. Taken together, our results establish TRPC3 as a new type of postsynaptic channel that mediates mGluR-dependent synaptic transmission in cerebellar Purkinje cells and is crucial for motor coordination.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Animals
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Behavior, Animal / physiology
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Calcium / metabolism
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Cerebellum / cytology
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Electric Stimulation / methods
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Excitatory Postsynaptic Potentials / radiation effects
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In Vitro Techniques
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Methoxyhydroxyphenylglycol / analogs & derivatives
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Methoxyhydroxyphenylglycol / pharmacology
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Mice
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Mice, Knockout
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Nerve Tissue Proteins / metabolism
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Neural Pathways / physiology
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Neural Pathways / radiation effects
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Patch-Clamp Techniques / methods
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Psychomotor Performance / drug effects
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Psychomotor Performance / physiology*
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Purkinje Cells / physiology
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Synaptic Transmission / physiology*
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TRPC Cation Channels / deficiency
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TRPC Cation Channels / genetics
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TRPC Cation Channels / physiology*
Substances
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Nerve Tissue Proteins
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TRPC Cation Channels
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TRPC3 cation channel
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Methoxyhydroxyphenylglycol
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6-Cyano-7-nitroquinoxaline-2,3-dione
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Calcium
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3,4-dihydroxyphenylglycol