Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1

Article

关键词: LONG-TERM DEPRESSION;    SYNAPTIC ACTIVATION;    CEREBELLAR;    CONDUCTANCE;    RELEASE;    DEFICIT;    HOMER;   

DOI  :  10.1038/nature02162

来源: SCIE

【 摘 要 】

Group I metabotropic glutamate receptors (consisting of mGluR1 and mGluR5) are G-protein-coupled neurotransmitter receptors(1) that are found in the perisynaptic region of the postsynaptic membrane(2). These receptors are not activated by single synaptic volleys but rather require bursts of activity(3-5). They are implicated in many forms of neural plasticity including hippocampal long-term potentiation and depression(6-8), cerebellar long-term depression(8-11), associative learning(7,11), and cocaine addiction(12). 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(4,5,13-15). 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.

【 授权许可】

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