Reduction of Ventricular Sodium Current in a Mouse Model of HIV
Bibliographic record
Abstract
INTRODUCTION: Cardiac arrhythmias have been reported in AIDS patients. Arrhythmias can arise from alterations in ventricular Na(+) channel function. However, it is unknown whether HIV affects cardiac Na(+) channel function. Therefore, the purpose of this study was to characterize the effect of HIV on ventricular Na(+) current (I(Na)) in a transgenic model of HIV (CD4C/HIV mice), which exhibit a severe AIDS-like disease. METHODS AND RESULTS: Patch-clamp techniques were used to examine I(Na) and action potentials (AP) in ventricular myocytes isolated from HIV and wild-type (WT) mice. In HIV myocytes peak I(Na) was reduced (at -50 mV: HIV, -55.3 +/- 4.3 pA/pF, n = 15; WT, -79.4 +/- 5.2 pA/pF, n = 16, P < 0.05), whereas late I(Na) was similar in both groups (HIV, -4.3 +/- 0.4 pA/pF; WT, -4.4 +/- 0.4 pA/pF, n = 22/group). AP amplitude (HIV 91.5 +/- 4.7 mV, n = 12; WT 104.4 +/- 3.1 mV, n = 15, P < 0.05) and the maximal velocity of the AP upstroke (V(max); HIV, 57.2 +/- 9.3 mV/ms, n = 12; WT, 113.5 +/- 8 mV/ms, n = 15, P < 0.05) were decreased in HIV myocytes. ECG recordings revealed that the QRS complex was prolonged in HIV mice (HIV, 15.7 +/- 0.2 ms, n = 22; WT, 14.1 +/- 0.5 ms, n = 10, P < 0.05). The serum levels of interleukin-1beta were elevated in HIV mice (HIV, 18.1 +/- 3.1 pg/mL, n = 3; WT, 5.1 +/- 1.1 pg/mL, n = 4, P < 0.05) in line with previous evidence that suggests that elevated levels of cytokines can affect cardiac ion currents. CONCLUSION: Overall, our observations suggest that elevated levels of proinflammatory cytokines in CD4C/HIV mice could alter Na(+) channel function, thus altering cardiac depolarization and contribute to the generation of arrhythmias.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| 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) | 0.000 | 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 teacher head, 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".