title: TRPC3 channels are required for synaptic transmission and motor coordination.
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.
authors.affiliation: Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, 80802 Munich, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Hartmann
authors.forename: Elena
authors.initials: E
authors.lastname: Dragicevic
authors.forename: Helmuth
authors.initials: H
authors.lastname: Adelsberger
authors.forename: Horst A
authors.initials: HA
authors.lastname: Henning
authors.forename: Martin
authors.initials: M
authors.lastname: Sumser
authors.forename: Joel
authors.initials: J
authors.lastname: Abramowitz
authors.forename: Robert
authors.initials: R
authors.lastname: Blum
authors.forename: Alexander
authors.initials: A
authors.lastname: Dietrich
authors.forename: Marc
authors.initials: M
authors.lastname: Freichel
authors.forename: Veit
authors.initials: V
authors.lastname: Flockerzi
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.forename: Arthur
authors.initials: A
authors.lastname: Konnerth
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D050052:TRPC Cation Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D008734:Methoxyhydroxyphenylglycol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002118:Calcium; C010117:3,4-dihydroxyphenylglycol