Differential Alterations of Receptor Densities of Three Muscarinic Acetylcholine Receptor Subtypes and Current Densities of the Corre-sponding K<sup>+</sup> Channels in Canine Atria with Atrial Fibrillation Induced by Experimental Congestive Heart Failure
Bibliographic record
Abstract
Parasympathetic tone and congestive heart failure (CHF) are two of promoting factors in initiation and perpetuation of atrial fibrillation (AF). Recent studies indicate co-existence of multiple muscarinic acetylcholine receptor subtypes (mAChRs) that mediate several distinct K+ currents in the heart; inward rectifier K+ current IKACh by the M2, and two delayed rectifier K+ currents IKM3 and IK4AP by the M3 and M4 receptors, respectively. We studied the alterations of atrial mAChRs and their coupled K+ channels in the setting of AF in dogs with ventricular tachypacing-induced CHF. Whole-patch-clamp recordings showed that the current densities of IKACh (induced by 1 mM acetylcholine) and IK4AP (induced by 1 mM 4-aminopyridine) were ñ45% and ñ55% lower, respectively, while that of IKM3 (induced by 10 mM choline) was ñ75% higher, at a plateau voltage of 0 mV in atrial myocytes from CHF than those from healthy hearts. In healthy hearts, IKACh comprised >60%, and IKM3 and IK4AP <30%, of the total outward K+ currents mediated by mAChRs at depolarized potentials (between -20 mV and +50 mV). In AF atria of CHF dogs, however, the contribution of IKM3 increased to approximately 50%, exceeding those of IKACh or IK4AP. Western blot analyses with atrial membrane protein samples indicated that receptor densities of the M2 and M4 subtypes decreased by approximately 33% and approximately 22%, respectively, whereas that of the M3 subtype increased by approximately 2.3 folds, in parallel to the alterations of the corresponding K+ currents. We conclude that differential alterations of mAChR subtypes underlie differential alterations of their coupled K+ channels in AF atria and these differential alterations may contribute to atrial remodeling in AF induced in the setting of CHF.
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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 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".