Endogenous TRPC channels mediate Ca2+ signals and trigeminal synaptic plasticity induced by mGluR5a

Abstract Aims Metabotropic glutamate receptor 5 (mGluR5), a member of group I mGluR, exerts its effect via elevation of intracellular Ca 2+ level. We here characterized Ca 2+ signals in the tsA201 cells transfected with mGluR5 and investigated the role of passages for mGluR5-induced Ca 2+ signals in synaptic plasticity. Main methods Using a genetically encoded Ca 2+ indicator, GCamp2, Ca 2+ signals were reliably induced by bath application of ( S )-3,5-dihydroxyphenylglycine, the group I mGluR agonist, in the tsA201 cells transfected with mGluR5. Using whole-cell recordings in the substantia gelatinosa (SG) neurons of the spinal trigeminal subnucleus caudalis (Vc), excitatory postsynaptic currents were recorded by stimulating the trigeminal tract. Key findings Ca 2+ signals were mediated by “classical” or “canonical” transient receptor potential (TRPC) channels, particularly TRPC1/3/4/6, but not TRPC5, naturally existing in the tsA201 cells. Interestingly, the induction of Ca 2+ signals was independent of the phospholipase C signaling pathway; instead, it critically involves the cyclic adenosine diphosphate ribose/ryanodine receptor-dependent signaling pathway and only partially protein kinase C. On the other hand, both TRPC3 and TRPC4 mediated mGluR1/5-induced long-lasting potentiation of excitatory synaptic transmission from the trigeminal primary afferents to the SG neurons of the Vc. Significance This study demonstrates that endogenous TRPC channels contribute to mGluR5-induced Ca 2+ signals in tsA201 cells and synaptic plasticity at excitatory synapses.