N-type calcium channel blockade: a new approach to preventing sudden cardiac death?
Bibliographic record
Abstract
This editorial refers to ‘Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure’ by Y. Yamada et al. , pp. 183–193, this issue. Congestive heart failure (CHF) is a major cause of death in the population, and sudden cardiac death (SCD) is a common terminal event in CHF.1 CHF patients have elevated resting sympathetic activity, and a simple carbohydrate meal can further raise their sympathetic nerve discharge rates to values characteristic of patients with acute myocardial infarction.2 Autonomic abnormalities play important roles in SCD due to ventricular tachyarrhythmias (VTs) resulting from a wide range of cardiac pathologies, including ischaemic heart disease, CHF, and genetic SCD syndromes.3 Classical antiarrhythmic drugs are ineffective in preventing CHF-associated SCD,4 whereas beta-adrenoceptor antagonists have significant value,1 emphasizing the importance of the autonomic nervous system in VTs related to CHF. A wide range of voltage-dependent Ca2+ channels have been described, including L-type Ca2+ channels (LTCCs) responsible for cardiac excitation–contraction coupling, T-type Ca2+ channels (TTCCs) involved in cardiac automaticity, and N-type neuronal Ca2+ channels (NTCCs).5 NTCCs, encoded by Cav2.2 (CACNA1B) subunits, are particularly involved in cardiovascular sympathetic regulation.6 In this issue of Cardiovascular Research , Yamada et al. 7 report the results of a fascinating series of experiments that evaluate the role of NTCCs and their inhibition in a model of CHF-associated SCD. The model involves mice engineered to produce cardiomyocyte-specific overexpression of a dominant-negative (dn) …
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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 | 0.005 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.008 |
| Insufficient payload (model declined to judge) | 0.000 | 0.002 |
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; both teacher heads agree on what is shown here.
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".