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.
Pubmed ID: 18701065 RIS Download
6-Cyano-7-nitroquinoxaline-2,3-dione | Animals | Behavior, Animal | Calcium | Cerebellum | Electric Stimulation | Excitatory Amino Acid Agonists | Excitatory Amino Acid Antagonists | Excitatory Postsynaptic Potentials | In Vitro Techniques | Methoxyhydroxyphenylglycol | Mice | Mice, Knockout | Nerve Tissue Proteins | Neural Pathways | Patch-Clamp Techniques | Psychomotor Performance | Purkinje Cells | Synaptic Transmission | TRPC Cation Channels