title: 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.
authors.affiliation: Department of Physiology, Nippon Dental University, School of Life Dentistry at Tokyo, Tokyo 102-8159, Japan. matsu-s@tky.ndu.ac.jp
authors.forename: Shigeji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Ryoji
authors.initials: R
authors.lastname: Ide
authors.forename: Chikako
authors.initials: C
authors.lastname: Saiki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects*; D004553:Electric Conductivity; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009620:Nodose Ganglion / Q000166:cytology*; D010042:Ouabain / Q000008:administration & dosage / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase