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

Life Sci. 2019 Aug 15:231:116567. doi: 10.1016/j.lfs.2019.116567. Epub 2019 Jun 13.

Abstract

Aims: 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.

Main methods: 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.

Key findings: 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.

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

Keywords: Ca(2+) signal; Canonical transient receptor potential; Cyclic adenosine diphosphate ribose; GCamp2; Metabotropic glutamate receptor 5; Spinal trigeminal nucleus caudalis; Synaptic plasticity.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • Calcium Signaling / physiology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials
  • Female
  • Long-Term Potentiation / drug effects
  • Male
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Metabotropic Glutamate 5 / metabolism*
  • Receptors, Metabotropic Glutamate / metabolism
  • Synapses / metabolism
  • Synaptic Transmission
  • TRPC Cation Channels / metabolism*
  • Trigeminal Nerve / metabolism
  • Trigeminal Nucleus, Spinal / metabolism

Substances

  • Calcium Channels
  • Excitatory Amino Acid Antagonists
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • TRPC Cation Channels
  • metabotropic glutamate receptor type 1
  • Calcium