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T‐type Ca <sup>2+</sup> Channels and The Induction of CICR in Vascular Smooth Muscle

2012· article· en· W3174610915 on OpenAlexaffabout
Kamran Bigdely‐Shamloo, Edward J. Vigmond, Donald G. Welsh

Bibliographic record

VenueThe FASEB Journal · 2012
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCaveolin-1 and cellular processes
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsRyanodine receptorBiophysicsChemistryDepolarizationEndoplasmic reticulumVoltage-dependent calcium channelSERCACalciumBiologyBiochemistry

Abstract

fetched live from OpenAlex

Recent work has revealed a microdomain in cerebral arterial smooth muscle comprised of caveoli and sarcoplasmic reticulum. Immunolabeling techniques indicate that T‐type Ca 2+ channels and ryanodine receptors localize to this microdomain while L‐type Ca 2+ channels do not. Given these observations, T‐type Ca 2+ channels were hypothesized to initiate a CICR‐like response. To address this hypothesis, a model of smooth muscle Ca 2+ handling was developed. Our physical model was derived from direct dimensional measurements and consisted of a large cytosolic domain and a structured subspace of caveoli and SR. T‐type Ca 2+ channels and ryanodine receptors were localized to the subspace whereas L‐type Ca 2+ channels, Na + /Ca 2+ exchanger, PMCA and SERCA pump were placed outside this region. The kinetics of SR Ca 2+ uptake/release were derived from previous models. The activity of sacrolemmal pumps, exchanges and channels were obtained from various sources and scaled in a smooth muscle specific manner. A 20 mV depolarizing step from −60 mV induced an initial CICR process that gave way to periodic SR Ca 2+ release every 10sec. This spark‐like release pattern was dependent upon continuous Ca 2+ influx through T‐type Ca 2+ channels and the recovery of ryanodine receptors from Ca 2+ ‐induced inactivation. Varying the depolarizing step from −50 to −30 mV did not affect the frequency of SR release, a finding consist with T‐type Ca 2+ channels acting as a two‐state switch. Supported by the Canadian Institute for Health Research.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.040
Threshold uncertainty score0.190

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 head0.011
GPT teacher head0.224
Teacher spread0.213 · 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 teacher head, 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
Published2012
Admission routes2
Has abstractyes

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