Activation of native TRPC3 cation channels by phospholipase D.
In the mammalian nervous system, stimulation of G-protein-coupled type I glutamate receptors triggers various forms of neuronal plasticity, including cerebellar long-term depression and hippocampal long-term potentiation. Activation of these receptors in the cerebellum also leads to a slow excitatory postsynaptic current mediated by nonselective TRPC3 cation channels. How TRPC3 channels are opened is unknown, although it is widely thought that channel gating requires phospholipase C activation. Using the patch-clamp technique and immunohistochemistry in rat cerebellar slices, we show that metabotropic glutamate receptors activate TRPC3 channels through the small GTP-binding protein Rho and subsequent phospholipase D stimulation. TRPC3 channel gating is independent of phospholipase C activity. These results reveal a new mechanism for the gating of the ubiquitous TRPC3 channel and identify a key role for phospholipase D in the generation of the slow excitatory postsynaptic current in cerebellar Purkinje cells.
Glitsch
Maike D
MD
Department of Physiology, Anatomy, and Genetics, Oxford University, Parks Road, Oxford, UK. maike.glitsch@dpag.ox.ac.uk
D020001:1-Butanol / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D018408:Patch-Clamp Techniques; D010739:Phospholipase D / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D018094:Receptors, Metabotropic Glutamate; D011994:Recombinant Proteins; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C104077:metabotropic glutamate receptor type 1; D020001:1-Butanol; D010738:Type C Phospholipases; D010739:Phospholipase D; C106801:phospholipase D1; D020741:rho GTP-Binding Proteins