TRPC3 channels are required for synaptic transmission and motor coordination.
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.
Hartmann
Jana
J
Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, 80802 Munich, Germany.
Dragicevic
Elena
E
Adelsberger
Helmuth
H
Henning
Horst A
HA
Sumser
Martin
M
Abramowitz
Joel
J
Blum
Robert
R
Dietrich
Alexander
A
Freichel
Marc
M
Flockerzi
Veit
V
Birnbaumer
Lutz
L
Konnerth
Arthur
A
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*
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