Kir2.4 and Kir2.1 K<sup>+</sup> channel subunits co‐assemble: a potential new contributor to inward rectifier current heterogeneity
Bibliographic record
Abstract
Heteromeric channel assembly is a potential source of physiological variability. The potential significance of Kir2 subunit heterotetramerization has been controversial, but recent findings suggest that heteromultimerization of Kir2.1-3 may be significant. This study was designed to investigate whether the recently described Kir2.4 subunit can form heterotetramers with the important subunit Kir2.1, and if so, to investigate whether the resulting heterotetrameric channels are functional. Co-expression of either dominant negative Kir2.1 or Kir2.4 subunits in Xenopus oocytes with either wild-type Kir2.1 or 2.4 strongly decreased resulting current amplitude. To examine physical association between Kir2.1 and Kir2.4, Cos-7 cells were co-transfected with a His(6)-tagged Kir2.1 subunit (Kir2.1-His(6)) and a FLAG-tagged Kir2.4 subunit (Kir2.4-FLAG). After pulldown with a His(6)-binding resin, Kir2.4-FLAG could be detected in the eluted cell lysate by Western blotting, indicating co-assembly of Kir2.1-His(6) and Kir2.4-FLAG. Expression of a tandem construct containing covalently linked Kir2.1 and 2.4 subunits led to robust current expression. Kir2.1-Kir2.4 tandem subunit expression, as well as co-injection of Kir2.1 and Kir2.4 cRNA into Xenopus oocytes, produced currents with barium sensitivity greater than that of Kir2.1 or Kir2.4 subunit expression alone. These results show that Kir2.4 subunits can co-assemble with Kir2.1 subunits, and that co-assembled channels are functional, with properties different from those of Kir2.4 or Kir2.1 alone. Since Kir2.1 and Kir2.4 mRNAs have been shown to co-localize in the CNS, Kir2.1 and Kir2.4 heteromultimers might play a role in the heterogeneity of native inward rectifier currents.
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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 | 0.000 | 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) | 0.000 | 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".