Electrophysiological Characterization of Cardiac Muscarinic Acetylcholine Receptors: Different Subtypes Mediate Different Potassium Currents
Bibliographic record
Abstract
To characterize electrophysiologically the K+ currents mediated by various mAChR subtypes, we performed detailed whole-cell patch-clamp studies in canine atrial myocytes. I(KACh) was induced by 1 mM ACh (acetylcholine) or by arecaidine but-2-ynyl ester tosylate (100 nM, an M2 receptor selective agonist) and was blocked by methoctramine (20 nM, an M2 receptor selective antagonist). Tetramethylammonium (0.5 mM) activated a K+ conductance with delayed rectifying properties (I(KM3)) and the currents were highly sensitive to 4-diphenylacetoxy-N-methylpiperidine methiodide (2 nM, an M3 receptor inhibitor). 4-aminopyridine (1 mM) induced a delayed rectifier-like current (I(K4AP)) which was selectively suppressed by tropicamide (200 nM, an M4 receptor blocker). The current waveforms, I-V relationships, steady-state voltage-dependence, kinetics and pharmacological properties of these three currents were different from one another and distinct from the classical delayed rectifier K+ currents (I(Kr) and I(Ks)). Both I(KACh) and I(K4AP) were sensitive to pertussis ntoxin, whereas I(KM3) was not. Isoproterenol (1 mM) markedly depressed I(KM3), but increased I(K4AP) and did not alter I(KACh). The effects of isoproterenol were reversed by propranolol (1 mM); and ACh completely suppressed I(KM3) and I(K4AP). The results suggest that the K+ currents mediated by different subtypes of mAChR represent different populations of K+ channels and that the cholinergic regulation of the heart's electrical function is a consequence of activating multiple mAChRs linked to different effector systems with potentially varying signal transduction.
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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 | 0.000 |
| 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 | 0.000 |
| 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 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".