Abstract Mo058: Cellular and Subcellular Ventricular Localization of the Fast Transient Outward Potassium Channels in the Murine Heart
Bibliographic record
Abstract
Introduction: Cardiac fast transient outward potassium currents (Ito,f) are formed by KCND2 (Kv4.2) and KCND3 (Kv4.3) channels in mice and primarily KCND3 in humans. Rapid Ito,f activation induces early phase 1 repolarization of action potentials (APs), which has been linked strongly to the modulation of excitation-contraction coupling (ECC). Consequently, variations in Ito,f densities underlie regional differences in ventricular APs and myocardial contractile properties. To investigate further the role of Ito,f in cardiac function, we created mice with fluorescently labelled KCND2 (KCND2-GFP) and KCND3 (KCND3-RFP). Methods and Results: The expression patterns of Ito,f in the ventricles were examined using frozen histological sections. Remarkably, KCND2 and KCND3 were preferentially localized to the intercalated discs (ICDs) by >50%, with expression also in lateral membranes and within t-tubules (i.e. a sarcomeric pattern), yet KCND3 showed a greater t-tubule localization. Additionally, KCND2 expression was, as expected, greater (P<0.048, two-way ANOVA; n=3) in the epi- versus endo-myocardium of both ventricles, whereas KCND3 lacked (P>0.172; n=3) a distinct gradient. Moreover, KCND2 expression inversely correlated with the temporal sequence of ventricular activation, whereby the posterobasal regions that depolarize last show elevated Kv4.2 (P=0.009, unpaired t-test; n=3) compared to the anterolateral endocardium activated first. In contrast, Kv4.3 demonstrates a relatively uniform expression. Conclusions: The regional expression patterns of Ito,f in ventricles and preferential Ito,f expression in t-tubules support previous studies suggesting that Ito,f controls the regional variations in the timing and amplitude of ECC. We are currently exploring the possible differential actions of KCND2 versus KCND3 in ECC and the potential consequence of ICD localization of Ito,f on ephaptic coupling.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".