Effect of stimulation rate, sarcomere length and Ca<sup>2+</sup> on force generation by mouse cardiac muscle
Bibliographic record
Abstract
The relations between stress, stimulation rate and sarcomere length (SL) were investigated in 24 cardiac trabeculae isolated from right ventricles of mice (CF-1 males, 25-30 g) and superfused with Hepes solution ([Ca(2+)](o) = 1 mM, pH 7.4, 25 degrees C). Stress and SL were measured by a strain gauge transducer and laser diffraction technique, respectively. Stress versus stimulation frequency formed a biphasic relation (25 degrees C, [Ca(2+)](o) = 2 mM) with a minimum at 0.7-1 Hz (~15 mN mm(-2)), a 150 % decrease from 0.1 to 1 Hz (descending limb) and a 75 % increase from 1 to 5 Hz (ascending limb). Ryanodine (0.1 microM) inhibited specifically the descending limb, while nifedipine (0.1 microM) affected specifically the ascending limb. This result suggests two separate sources of Ca(2+) for stress development: (1) net Ca(2+) influx during action potentials (AP); and (2) Ca(2+) entry into the cytosol from the extracellular space during diastolic intervals; Ca(2+) from both (1) and (2) is sequestered by the SR between beats. Raising the temperature to 37 degrees C lowered the stress-frequency relation (SFR) by approximately 0-15 mN mm(-2) at each frequency. Because the amount of Ca(2+) carried by I(Ca,L) showed a approximately 3-fold increase under the same conditions, we conclude that reduced Ca(2+) loading of the SR was probably responsible for this temperature effect. A simple model of Ca(2+) fluxes addressed the mechanisms underlying the SFR. Simulation of the effect of inorganic phosphates (P(i)) on force production was incorporated into the model. The results suggested that O(2) diffusion limits force production at stimulation rates >3 Hz. The stress-SL relations from slack length (approximately 1.75 microm) to 2.25 microm showed that the passive stress-SL curve of mouse cardiac trabeculae is exponential with a steep increase at SL >2.1 microm. Active stress (at 1 Hz) increased with SL, following a curved relation with convexity toward the abscissa at [Ca(2+)] = 2 mM. At [Ca(2+)] from 4 to 12 mM, the stress-SL curves superimposed and the relation became linear, which revealed a saturation step in the activation of force production. EC coupling in mouse cardiac muscle is similar to that observed previously in the rat, although important differences exist in the Ca(2+) dependence of force development. These results may suggest a lower capacity of the SR for buffering Ca(2+), which makes the generation of force in mouse cardiac ventricle more dependent on Ca(2+) entering during action potentials, particularly at high heart rate.
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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".