The RyR–Cl<sub>Ca</sub>–VDCC axis contributes to spontaneous tone in urethral smooth muscle
Bibliographic record
Abstract
Abstract Current therapies including pharmaceutical intervention and surgery have limited efficacy on stress urinary incontinence (SUI). One type of SUI is due to low intraurethral pressure caused by the disabled contraction of urethral smooth muscle (USM). However, the molecular mechanisms underlying the motility of USM remain unknown. Here, we show that USM represents spontaneous tone after stretching in humans and mice. Deletion of TMEM16A in the smooth muscle of mice abolishes spontaneous urethral tone. Furthermore, ClCa currents and [Ca2+]i in TMEM16ASMKO mice were largely impaired. Inhibitors of ryanodine receptor (RyR), TMEM16A encoded calcium‐activated chloride channel (ClCa) and L‐type voltage‐dependent calcium channel (VDCC) fully prevented spontaneous tone accompanied by a significant decrease of intracellular calcium concentration ([Ca2+]i). In summary, RyR–ClCa–VDCC signaling contributes to spontaneous USM tone. This finding may provide a new promising approach for women with stress SUI who reject surgery.
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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 | 0.000 |
| 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".