TRPC6 expression in neurons is differentially regulated by NR2A- and NR2B-containing NMDA receptors

J Neurochem. 2017 Nov;143(3):282-293. doi: 10.1111/jnc.14215. Epub 2017 Oct 13.

Abstract

The expression of transient receptor potential canonical 6 (TRPC6) in central nervous system (CNS) is important for neuronal functions and certain neural disorders. However, the regulatory mechanism of TRPC6 expression in neurons is still obscure. In this study, we show that TRPC6 expression in the primary cultured cortical neurons is bidirectionally regulated by glutamate. Activation of NR2A-containing NMDARs induces TRPC6 transcription through a calcineurin-dependent pathway. In contrast, activation of NR2B-containing NMDARs causes TRPC6 degradation through calpain. Thus, TRPC6 expression in neurons is regulated by glutamate in a bidirectional manner that is dependent on NR2A and NR2B.

Keywords: NMDA receptors; TRPC6; calcineurin; calpain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cyclosporine / pharmacology
  • Dipeptides / pharmacology
  • Embryo, Mammalian
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agents / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Neurons / drug effects
  • Neurons / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Spectrin / genetics
  • Spectrin / metabolism
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • Time Factors

Substances

  • Dipeptides
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agents
  • NR2A NMDA receptor
  • NR2B NMDA receptor
  • RNA, Small Interfering
  • Receptors, N-Methyl-D-Aspartate
  • TRPC Cation Channels
  • Trpc6 protein, rat
  • Spectrin
  • calpeptin
  • Cyclosporine