Cardiac contraction, calcium transients, and myofilament calcium sensitivity fluctuate with the estrous cycle in young adult female mice
Bibliographic record
Abstract
This study established conditions to induce regular estrous cycles in female C57BL/6J mice and investigated the impact of the estrous cycle on contractions, Ca2+ transients, and underlying cardiac excitation-contraction (EC)-coupling mechanisms. Daily vaginal smears from group-housed virgin female mice were stained to distinguish estrous stage (proestrus, estrus, metestrus, diestrus). Ventricular myocytes were isolated from anesthetized mice. Contractions and Ca2+ transients were measured simultaneously (4 Hz, 37 °C). Interestingly, mice did not exhibit regular cycles unless they were exposed to male pheromones in bedding added to their cages. Field-stimulated myocytes from mice in estrus had larger contractions (∼2-fold increase), larger Ca2+ transients (∼1.11-fold increase), and longer action potentials (>2-fold increase) compared with other stages. Larger contractions and Ca2+ transients were not observed in estrus myocytes voltage-clamped with shorter action potentials. Voltage-clamp experiments also demonstrated that estrous stage had no effect on Ca2+ current, EC-coupling gain, diastolic Ca2+, sarcoplasmic reticulum (SR) Ca2+ content, or fractional release. Although contractions were largest in estrus, myofilament Ca2+ sensitivity was lowest (EC50 values ∼1.15-fold higher) in conjunction with increased phosphorylation of myosin binding protein C in estrus. Contractions were enhanced in ventricular myocytes from mice in estrus because action potential prolongation increased SR Ca2+ release. These findings demonstrate that cyclical changes in reproductive hormones associated with the estrous cycle can influence myocardial electrical and contractile function and modify Ca2+ homeostasis. However, such changes are unlikely to occur in female mice housed in groups under conventional conditions, since these mice do not exhibit regular estrous cycles.
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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 | 0.001 | 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".