Direct inhibition of the transient voltage-gated K(+) currents mediates the excitability of tetrodotoxin-resistant neonatal rat nodose ganglion neurons after ouabain application

Eur J Pharmacol. 2011 Jun 1;659(2-3):130-8. doi: 10.1016/j.ejphar.2011.01.037. Epub 2011 Feb 4.

Abstract

The purpose of the present study was to determine the relationship between the responses of transient and sustained K(+) currents, and action potentials to ouabain, and to compare the immunoreactive expression of alpha Na(+)-K(+)-ATPase isoforms (α(1), α(2) and α(3)) in neonatal rat small-diameter nodose ganglion neurons. We used perforated patch-clamp techniques. We first confirmed that the neurons (n=20) were insensitive to 0.5 μM tetrodotoxin (TTX). Application of 1 μM ouabain 1) decreased the transient K(+) currents in 60% of neurons and the sustained K(+) currents in 20%, 2) increased voltage-gated transient and sustained K(+) currents in 20% of neurons, and 3) had no effect on transient K(+) currents in 20% of neurons and on sustained K(+) currents in 60%. Thirteen of the neurons were of a rapidly adapting type, and the remaining 7 were of a slowly adapting type. In 6 rapidly adapting type neurons (46%), their activity was not significantly altered by ouabain application, but in 4 rapidly adapting type neurons, the activity increased. In the remaining 3 rapidly adapting type neurons, ouabain application hyperpolarized the resting membrane potential. The slowly adapting type 7 neurons each showed increased activity after 1 μM ouabain application. The α(1) isoform of Na(+)-K(+)-ATPase was identified as the predominant immunoreactive isoforms in small-diameter nodose ganglion neurons. These results suggest that the increased activity of small-diameter nodose ganglion neurons seen after application of 1 μM ouabain is mediated by direct inhibition of the transient K(+) current.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Animals, Newborn
  • Dose-Response Relationship, Drug
  • Drug Resistance / drug effects*
  • Electric Conductivity*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Ion Channel Gating / drug effects
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Nodose Ganglion / cytology*
  • Ouabain / administration & dosage
  • Ouabain / pharmacology*
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors*
  • Potassium Channels, Voltage-Gated / metabolism
  • Protein Subunits / metabolism
  • Rats
  • Sodium Channel Blockers / pharmacology
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Tetrodotoxin / pharmacology*
  • Time Factors

Substances

  • Potassium Channels, Voltage-Gated
  • Protein Subunits
  • Sodium Channel Blockers
  • Tetrodotoxin
  • Ouabain
  • Sodium-Potassium-Exchanging ATPase