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Nitric oxide activates hypoglossal motoneurons by cGMP‐dependent inhibition of TASK channels and cGMP‐independent activation of HCN channels

2012· article· en· W3176207377 on OpenAlexaff
Ian C. Wenker, Xinnian Chen, Hattie Liu, Richard L. Horner, Daniel K. Mulkey

Bibliographic record

VenueThe FASEB Journal · 2012
Typearticle
Languageen
FieldNeuroscience
TopicNeuroscience of respiration and sleep
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsChemistryNitric oxideDepolarizationHyperpolarization (physics)AfterhyperpolarizationBiophysicsPatch clampMembrane potentialCurrent clampElectrophysiologyCharybdotoxinAntagonistGatingVoltage clampNeuroscienceBiochemistryReceptorBiologyStereochemistry

Abstract

fetched live from OpenAlex

Nitric oxide (NO) is an important signaling molecule; however mechanism(s) underlying NO modulation of motoneurons (MNs) remain obscure. Here, we used a combination of in vivo and in vitro recording techniques to examine NO modulation of MNs in the hypoglossal motor nucleus (HMN). Microperfusion of DEA (NO donor) into the HMN of anesthetized adult rats increased genioglossus muscle activity. In the brain slice, whole‐cell current‐clamp recordings from hypoglossal MNs show that exposure to DEA depolarized membrane potential and increased responsiveness to depolarizing current injections. Under voltage‐clamp conditions, we found that NO inhibited a Ba 2+ ‐sensitive background K + conductance and activated a Cs + ‐sensitive hyperpolarization‐activated inward current (Ih). The NO‐sensitive K + conductance exhibited properties similar to TWIK‐related acid‐sensitive K + (TASK) channels and was blocked by ODQ (soluble guanylyl cyclase antagonist) and KT5823 (PKG antagonist). In Ba 2+ , NO activated both the instantaneous (Iinst) and time‐dependent (Iss) components of Ih. Interestingly, at more hyperpolarized potentials NO preferentially increased Iinst, and this was retained in ODQ but blocked by a cysteine‐specific oxidant. These results suggest that NO activates hypoglossal MNs by cGMP‐dependent inhibition of a TASK‐like current and S‐nitrosylation‐ dependent activation of Ih.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.031
GPT teacher head0.259
Teacher spread0.228 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2012
Admission routes1
Has abstractyes

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