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

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.