Cell Membrane Expression of Cardiac Sodium Channel Na<sub>v</sub>1.5 Is Modulated by α-Actinin-2 Interaction
Bibliographic record
Abstract
Cardiac sodium channel Na(v)1.5 plays a critical role in heart excitability and conduction. The molecular mechanism that underlies the expression of Na(v)1.5 at the cell membrane is poorly understood. Previous studies demonstrated that cytoskeleton proteins can be involved in the regulation of cell surface expression and localization of several ion channels. We performed a yeast two-hybrid screen to identify Na(v)1.5-associated proteins that may be involved in channel function and expression. We identified alpha-actinin-2 as an interacting partner of the cytoplasmic loop connecting domains III and IV of Na(v)1.5 (Na(v)1.5/LIII-IV). Co-immunoprecipitation and His(6) pull-down assays confirmed the physical association between Na(v)1.5 and alpha-actinin-2 and showed that the spectrin-like repeat domain is essential for binding of alpha-actinin-2 to Na(v)1.5. Patch-clamp studies revealed that the interaction with alpha-actinin-2 increases sodium channel density without changing their gating properties. Consistent with these findings, coexpression of alpha-actinin-2 and Na(v)1.5 in tsA201 cells led to an increase in the level of expression of Na(v)1.5 at the cell membrane as determined by cell surface biotinylation. Lastly, immunostaining experiments showed that alpha-actinin-2 was colocalized with Na(v)1.5 along the Z-lines and in the plasma membrane. Our data suggest that alpha-actinin-2, which is known to regulate the functional expression of the potassium channels, may play a role in anchoring Na(v)1.5 to the membrane by connecting the channel to the actin cytoskeleton network.
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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".