RGS4 attenuates parasympathetic signaling in the sinoatrial node: implications for heart rate regulation
Bibliographic record
Abstract
Parasympathetic signaling in the SAN is mediated by ACh‐dependent stimulation of M2 muscarinic receptors that are coupled to the heterotrimeric G‐protein subunits Giα and GoÎ±ï€ in the SA node. RGS proteins are potent inhibitors of G‐protein signaling. The RGS family members that regulate parasympathetic signaling in pacemaker cells are unknown. We here provide evidence that RGS4 is required for normal inhibition of parasympathetic control of sinus rhythm. Real time RT‐PCR shows that RGS4 is expressed at higher levels in the SAN compared to right atrium. Moreover, the LacZ staining pattern of hearts and right atria from Rgs4tm1Dgen/J knockout/reporter mice indicates robust and selective expression of RGS4 in the SAN. RGS4‐deficient animals showed significantly lower basal heart rates than wild type controls and greater heart rate increases following systemic atropine administration. Lastly, retrograde perfused hearts from RGS4‐deficient mice showed prolonged recovery kinetics following carbachol washout. Taken together these data indicate greater parasympathetic control of heart rate in the knockout strain, and suggest an important role for RGS4 in the normal inhibition of parasympathetic signaling and regulation of sinus rhythm in the mouse heart.
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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) | 0.000 | 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) | 0.002 | 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".