Role of TRP channels in Gq-coupled protease-activated receptor 1-mediated activation of mouse nodose pulmonary C-fibers

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Abstract

We evaluated the mechanisms underlying protease-activated receptor 1 (PAR1)-mediated activation of nodose C-fibers in mouse lungs. The PAR1-induced action potential discharge at the terminals was strongly inhibited in phospholipase C-β3 (PLCβ3)-deficient animals. At the level of the cell soma, PAR1 activation led to an increase in cytosolic calcium that was largely inhibited by transient receptor potential (TRP) A1 antagonism. Patch-clamp recordings, however, revealed that neither TRPA1 nor TRPV1 or any other ruthenium red-sensitive ion channels are required for the PAR1-mediated inward current or membrane depolarization in isolated nodose neurons. Consistent with these findings, PAR1-mediated action potential discharge in mouse lung nodose C-fiber terminals was unaltered in Trpa1/Trpv1 double-knockout animals and Trpc3/Trpc6 double-knockout animals. The activation of the C-fibers was also not inhibited by ruthenium red at concentrations that blocked TRPV1- and TRPA1-dependent responses. The biophysical data show that PAR1/ Gq-mediated activation of nodose C-fibers may involve multiple ion channels downstream from PLCβ3 activation. TRPA1 is an ion channel that participates in PAR1/Gq-mediated elevation in intracellular calcium. There is little evidence, however, that TRPA1, TRPV1, TRPC3, TRPC6, or other ruthenium red-sensitive TRP channels are required for PAR1/Gq-PLCβ3-mediated membrane depolarization and action potential discharge in bronchopulmonary nodose C-fibers in the mouse.

Original languageEnglish (US)
Pages (from-to)L192-L199
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume318
Issue number1
DOIs
StatePublished - 2020

Keywords

  • Airway C-fiber
  • GPCR
  • Mouse nodose
  • Protease-activated receptor 1
  • TRP channel

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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