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Angiotensin II Inhibits T‐type Ca <sup>2+</sup> Channels in Cerebral Arterial Smooth Muscle Cells

2016· article· en· W4389008254 on OpenAlexaffabout
Ahmed M. Hashad, María Sancho, Donald G. Welsh

Bibliographic record

VenueThe FASEB Journal · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsUniversity of CalgaryWestern University
Fundersnot available
KeywordsAngiotensin IINADPH oxidaseLosartanChemistryPatch clampProtein kinase CVascular smooth muscleEndocrinologyInternal medicineMyocyteCerebral arteriesGq alpha subunitReactive oxygen speciesBiophysicsReceptorSignal transductionBiologyBiochemistryG proteinMedicineSmooth muscle

Abstract

fetched live from OpenAlex

T‐type Ca 2+ channels (Ca V 3.1 and Ca V 3.2) are expressed in cerebral arterial smooth muscle cells and they play a key role in regulating arterial tone. In this study, we investigated whether and by what mechanism Angiotensin II (Ang II), a vasoactive peptide produced within the cerebral arterial wall, influences T‐type Ca 2+ channels. Using patch clamp electrophysiology and rat cerebral arterial myocytes, Ang II (100 nM) was shown to inhibit T‐type Ca 2+ currents in a time‐dependent manner (~ 40% after 15 min); it also shifted the voltage‐dependency of activation by 7 mV. Ang II induced inhibition was mediated through the AT 1 receptor, as preincubation with Losartan (1 μM) abolished the effect. Protein kinase C (PKC) blockade by GF 109203X (100 nM) did not eliminate Ang II‐mediated inhibition, demonstrating that this signaling protein was not involved. In contrast, NADPH oxidase inhibitors abolished the inhibitory effect of Ang II revealing a role for reactive oxygen species (ROS) on T‐type Ca 2+ channels. To delineate if Ang II is targeting a particular T‐type channel, Ni 2+ (50 μM) was added to selectively block Ca V 3.2. In the presence of Ni 2+ , Ang II did not induce further inhibition of the residual current, indicating that Ang II was selectively targeting Ca V 3.2. In summary, Ang II inhibits Ca V 3.2 channels in cerebral myocytes through the generation of ROS. These findings suggest that T‐type channels are a regulatory target of vasoactive stimuli, known to facilitate the “constrictive” phenotype prevalent with cerebrovascular disease. Support or Funding Information Canadian Institutes of Health Research, Alberta Innovates Health Solutions, Vanier Graduate Scholarship (CIHR)

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 score0.002
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 head0.214
Teacher spread0.203 · 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
Published2016
Admission routes2
Has abstractyes

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