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Protein Kinase G Inhibits T‐type Ca <sup>2+</sup> Channels in Rat Cerebral Arteries

2013· article· en· W3168020009 on OpenAlexaff
Osama F. Harraz, Donald G. Welsh

Bibliographic record

VenueThe FASEB Journal · 2013
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordscGMP-dependent protein kinaseNifedipineProtein kinase AVasodilationChemistryPatch clampCerebral arteriesBiophysicsEndocrinologyInternal medicineKinaseCell biologyElectrophysiologyBiologyBiochemistryCalciumMitogen-activated protein kinase kinaseMedicine

Abstract

fetched live from OpenAlex

In rat cerebral arteries, T‐type Ca 2+ channels are suppressed by protein kinase A (PKA) signaling. In this study, we examine whether protein kinase G (PKG), another key vasodilatory pathway, exerts a similar or distinctive influence on this conductance. Using patch clamp electrophysiology and cerebral arterial smooth muscle cells from rat, we monitored an inward Ba 2+ current that was divisible into nifedipine‐sensitive and –insensitive components. The nifedipine‐insensitive conductance displayed properties reminiscent of T‐type Ca 2+ channels; faster activation and steady state inactivation particularly at hyperpolarized potentials. Intriguingly, agents that target key PKG signaling proteins altered T‐type Ca 2+ channel activity. In particular, activators of PKG signaling (db‐cGMP, Na nitroprusside, SNAP) suppressed T‐type currents and evoked a hyperpolarized shift in steady state inactivation. PKG inhibitors (KT5823, ODQ) masked this suppression while having no effect on basal T‐type activity. In contrast, PKG manipulations had no influence on the nifedipine‐sensitive L‐type conductance. Cumulatively, our findings support the emerging view that T‐type Ca 2+ channels are a key regulatory target of vasodilatory signaling pathways (i.e. PKG and PKA).

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 score0.004

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.011
GPT teacher head0.217
Teacher spread0.206 · 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

Citations0
Published2013
Admission routes1
Has abstractyes

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