Abstract 13190: Integrin Linked Kinase is Required for Integrity of Cardiac Ion Current and Electrophysiologic Function
Bibliographic record
Abstract
Introduction: The cardiac adaptor protein integrin-linked kinase (ILK) is a regulator of cardiac structure/function. This study investigated the ventricular cardiomyocyte ion channel/electrophysiological remodeling caused by cardiomyocyte-directed ILK deletion (ILK-KO) in mice. Methods: Mice expressing the mckCRE transgene and 2 loxP1-flanked ILK-alleles (ILK-KO) were compared to littermate controls (WT). Perforated and tight-seal patch clamp were used respectively to record action potentials (APs) and ion currents in isolate ventricular cardiomyocytes. Cardiac function was assessed by echocardiography and rhythms were recorded by 24 hr telemetry in conscious mice. Results: ILK-KO mice died suddenly (50% mortality at 8 wks and 100% mortality at 18 wks) with progressive dilated cardiomyopathy. Spontaneous ventricular tachyarrhythmias (VTs) were recorded in 60% (*P<0.001 vs WT) at 10 wks. At 5 wks, prior to cardiac dysfunction, ILK-KO increased action potential duration (APD) by 68%*. I CaL and I K1 were unchanged, but fast inactivating transient outward (I to,f ) and slowly inactivating delayed rectifier (I K,slow ) K currents were reduced by 40%* and 34%* respectively. At 10 wks, LV systolic, diastolic dimensions increased by 72%*, 31%* respectively and LVEF decreased by 42%*; I CaL , I K1 , I to,f and I K,slow were all significantly decreased (by 23%, 32%, 38%, 53% respectively). APD was increased by 114%* and EADs/triggered activity were recorded. To assess mechanisms of specific K + current interactions, ILK was immunoprecitated (IPed) from cardiomyocyte membranes and K + channel subunits detected by immunoblot (Figure). Kv4.2 co-IPed with ILK, indicating direct physical interaction; whereas Kv1.4, Kv4.3 and KChIP2 did not. Conclusions: Cardiomyocyte ILK-deletion causes dilated cardiomyopathy, extensive ionic remodeling, VT and sudden death. Early K + current changes and co-IP point to a specific interaction with Kv4.2 subunits in pathogenesis.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".