Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1.
Group I metabotropic glutamate receptors (consisting of mGluR1 and mGluR5) are G-protein-coupled neurotransmitter receptors that are found in the perisynaptic region of the postsynaptic membrane. These receptors are not activated by single synaptic volleys but rather require bursts of activity. They are implicated in many forms of neural plasticity including hippocampal long-term potentiation and depression, cerebellar long-term depression, associative learning, and cocaine addiction. When activated, group I mGluRs engage two G-protein-dependent signalling mechanisms: stimulation of phospholipase C and activation of an unidentified, mixed-cation excitatory postsynaptic conductance (EPSC), displaying slow activation, in the plasma membrane. Here we report that the mGluR1-evoked slow EPSC is mediated by the TRPC1 cation channel. TRPC1 is expressed in perisynaptic regions of the cerebellar parallel fibre-Purkinje cell synapse and is physically associated with mGluR1. Manipulations that interfere with TRPC1 block the mGluR1-evoked slow EPSC in Purkinje cells; however, fast transmission mediated by AMPA-type glutamate receptors remains unaffected. Furthermore, co-expression of mGluR1 and TRPC1 in a heterologous system reconstituted a mGluR1-evoked conductance that closely resembles the slow EPSC in Purkinje cells.
Kim
Sang Jeong
SJ
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA.
Kim
Yu Shin
YS
Yuan
Joseph P
JP
Petralia
Ronald S
RS
Worley
Paul F
PF
Linden
David J
DJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D046508:Culture Techniques; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D011233:Precipitin Tests; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D050052:TRPC Cation Channels; D014162:Transfection
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002118:Calcium; D015220:Calcium Channels; D005998:Glycine; D018091:Receptors, AMPA; D012118:Resorcinols; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; C079215:3,5-dihydroxyphenylglycine