Striatin knock out induces a gain of function of <scp>I<sub>Na</sub></scp> and impaired Ca<sup>2+</sup> handling in <scp>mESC</scp>‐derived cardiomyocytes
Bibliographic record
Abstract
Abstract Aim Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated. Methods We studied the role(s) of cardiac Strn gene ( STRN ) by comparing the functional properties of CMs, generated from Strn‐KO and isogenic WT mouse embryonic stem cell lines. Results The spontaneous beating rate of Strn‐KO CMs was faster than WT cells, and this correlated with a larger fast I Na conductance and no changes in I f . Paced (2–8 Hz) Strn‐KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in I CaL and I Kr . Motion video tracking analysis highlighted an altered contraction in Strn‐KO CMs; this was associated with a global increase in intracellular Ca 2+ , caused by an enhanced late Na + current density (I NaL ) and a reduced Na + /Ca 2+ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na + channel expression and a more dynamic microtubule network in Strn‐KO CMs than in WT. Indeed, incubation of Strn‐KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of I Na conductance toward WT levels. Conclusion Loss of STRN alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn‐related multi‐protein complexes. This leads to impaired microtubules dynamics and Na + channels trafficking to the plasma membrane, causing a global Na + and Ca 2+ enhancement.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
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 teacher head, 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".