Functional M<sub>3</sub> muscarinic acetylcholine receptors in mammalian hearts
Bibliographic record
Abstract
In contrast to most peripheral tissues where multiple subtypes of muscarinic acetylcholine receptor (mAChR) coexist, with each of them playing its part in the orchestra of parasympathetic innervation, the myocardium has been traditionally considered to possess a single mAChR subtype. Although there is much evidence to support the notion that one receptor subtype (M2) orchestrates myocardial muscarinic transduction, there is emerging evidence that M1 and M3 receptors are also expressed and are of potential physiological, pathophysiological and pharmacological relevance. Clarifying this issue has a profound impact on our thinking about the cholinergic control of the heart function and disease and approaches to new drug development for the treatment of heart disease associated with parasympathetic dysfunction. This review article presents evidence for the presence of the M3 receptor subtype in the heart, and analyzes the controversial data from published pharmacological, functional and molecular studies. The potential roles of the M3 receptors, in parasympathetic control of heart function under normal physiological conditions and in heart failure, myocardial ischemia and arrhythmias, are discussed. On the basis of these considerations, we have made some proposals concerning the future of myocardial M3 receptor research.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.003 |
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".