Excitation-Contraction Coupling II
Bibliographic record
Abstract
3683-Pos Board B411 TRIC-A Prevents Store-Overload Induced Calcium Release Through Interaction with the Cardiac Ryanodine Receptor Xinyu Zhou1, Ki Ho Park1, Pei-hui Lin1, Mingzhai Sun1, Zui Pan1, Miyuki Nishi2, S.R. Wayne Chen3, Hiroshi Takeshima2. The Ohio State University, COLUMBUS, OH, USA, Kyoto University, Kyoto, Japan, University of Calgary, Calgary, AB, Canada. TRIC-A and TRIC-B are trimeric intracellular cation channels located at the sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER) of multiple cell types. These channels regulate the permeability of K ions across the SR/ER and consequently the movement of Ca ions during excitation-contraction coupling. Previously we showed that genetic ablation of TRIC led to compromised K-permeability and Ca release across the SR membrane, supporting the hypothesis that TRIC could function as counter-ion channels that allows the flow of K ions into the SR during the acute phase of Ca release. In the absence of TRIC, overload of Ca inside the ER/SR causes instability of Ca storage and release, leading to stress-induced dysfunction of multiple tissues. Spontaneous Ca waves, also called store overload-induced Ca release (SOICR) mediated by the type 2 ryanodine receptor (RyR2), evoke ventricular tachyarrhythmia in individuals with heart failure. Our biochemical studies revealed that the carboxyl-tail domain of TRIC-A could interact with the RyR channel, suggesting the possibility that TRIC-A may directly regulate the Ca release activity. We found that TRIC-A, but not TRIC-B, prevented the appearance of SOICR in HEK293 cells expressing RyR2. Cytosolic Ca measurement by Fura-2 and ER luminal Ca measurement by D1ER revealed that expression of TRIC-A in HEK293 cells could prevent overload of Ca inside the ER by targeting the RyR2 channel function. Such effect was translated into suppression of SOICR. These effects appeared to be specific for TRIC-A, as co-expression of RyR2 with TRIC-B did not affect SOICR. Together, our data suggest that functional interaction between TRIC-A and RyR can modulate the Ca release process from internal stores and regulate Ca homeostasis across the ER/SR.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.052 | 0.017 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".