Endogenous TRPC channels mediate Ca²⁺ signals and trigeminal synaptic plasticity induced by mGluR5

Metabotropic glutamate receptor 5 (mGluR5), a member of group I mGluR, exerts its effect via elevation of intracellular Ca²⁺ level. We here characterized Ca²⁺ signals in the tsA201 cells transfected with mGluR5 and investigated the role of passages for mGluR5-induced Ca²⁺ signals in synaptic plasticity.

Using a genetically encoded Ca²⁺ indicator, GCamp2, Ca²⁺ 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.

Ca²⁺ 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 Ca²⁺ 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.

This study demonstrates that endogenous TRPC channels contribute to mGluR5-induced Ca²⁺ signals in tsA201 cells and synaptic plasticity at excitatory synapses.