Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons

PLoS One. 2018 Jun 21;13(6):e0199282. doi: 10.1371/journal.pone.0199282. eCollection 2018.

Abstract

Two-pore domain potassium channels (K2P) constitute major candidates for the regulation of background potassium currents in mammalian cells. Channels of the TREK subfamily are also well positioned to play an important role in sensory transduction due to their sensitivity to a large number of physiological and physical stimuli (pH, mechanical, temperature). Following our previous report describing the molecular expression of different K2P channels in the vagal sensory system, here we confirm that TREK channels are functionally expressed in neurons from the mouse nodose ganglion (mNG). Neurons were subdivided into three groups (A, Ah and C) based on their response to tetrodotoxin and capsaicin. Application of the TREK subfamily activator riluzole to isolated mNG neurons evoked a concentration-dependent outward current in the majority of cells from all the three subtypes studied. Riluzole increased membrane conductance and hyperpolarized the membrane potential by approximately 10 mV when applied to resting neurons. The resting potential was similar in all three groups, but C cells were clearly less excitable and showed smaller hyperpolarization-activated currents at -100 mV and smaller sustained currents at -30 mV. Our results indicate that the TREK subfamily of K2P channels might play an important role in the maintenance of the resting membrane potential in sensory neurons of the autonomic nervous system, suggesting its participation in the modulation of vagal reflexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Capsaicin / pharmacology
  • Cells, Cultured
  • Humans
  • Ion Channel Gating / drug effects*
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nodose Ganglion / cytology*
  • Potassium Channels, Tandem Pore Domain / antagonists & inhibitors
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Riluzole / pharmacology*
  • Tetrodotoxin / toxicity

Substances

  • Potassium Channels, Tandem Pore Domain
  • Tetrodotoxin
  • Riluzole
  • Capsaicin

Grants and funding

This work was supported by grants to J.A.L. from the Spanish Government: Secretaría de Estado de Investigación, Desarrollo e Innovación (MINECO, BFU2014-58999-P), Galician Government: Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (GPC2015/022) and European Regional Development Fund (FP7-316265-BIOCAPS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.