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
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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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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 it