Abstract 809: Chronic Testosterone Deficiency Increases Late Inward Sodium Current in Ventricular Myocytes from Aging Male C57BL/6 Mice
Bibliographic record
Abstract
Clinical studies suggest that testosterone modulates the electrical activity of the heart and that low testosterone promotes cardiac arrhythmias. Here we investigated cellular mechanisms involved in the electrophysiological effects of chronic testosterone deficiency on the heart in aging male mice. Male C57BL/6 mice were subjected to either a gonadectomy (GDX) or a sham surgery at 1 month of age and then aged to 16-18 months. Ventricular myocytes were isolated and transmembrane voltage plus ionic currents were recorded with microelectrodes (20-25 MΩ; current clamp & discontinuous single electrode voltage clamp; 37 o C). Cells were paced at 2 and 4 Hz. Action potential duration at 90% repolarization (APD 90 ) was prolonged by GDX (57.9 ± 1.7 vs 108.2 ± 14.1 msec; p<0.05), while APD 50 and resting membrane potential were unchanged. We next determined whether an increase in late inward sodium current (I Na-L ) contributed to the increase in APD 90 in GDX cells. Voltage clamp studies showed that I Na-L was significantly larger in GDX cells compared to sham cells (-0.70 ± 0.16 vs -1.53 ± 0.27 pA/pF; p<0.05). When myocytes were superfused with the I Na-L antagonist ranolazine (10 μM), the increase in APD 90 was blocked in cells from GDX mice, so that APD 90 no longer differed between the two groups. By contrast, ranolazine had no effect on either APD 50 or resting membrane potential. Ranolazine also blocked the increase in I Na-L in cells from GDX mice. Prolongation of the action potential in GDX myocytes was associated with a significant increase in the incidence of early afterdepolarizations (EADs) when compared to sham controls. EADs were also inhibited by ranolazine. These data demonstrate that long-term GDX prolongs APD 90 at least in part by increasing the magnitude of I Na-L . These findings also suggest that an increase in I Na-L may promote arrhythmias in older men with low circulating testosterone levels.
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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) | 0.001 | 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) | 0.004 | 0.001 |
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".