Extracellular K <sup>+</sup> Is a Prerequisite for the Function and Plasma Membrane Stability of HERG Channels
Bibliographic record
Abstract
RATIONALE: The human ether-a-go-go-related gene (HERG) encodes the pore-forming subunits of the rapidly activating delayed rectifier potassium channel (I(Kr)) that is important for cardiac repolarization. Dysfunction of HERG causes long QT syndrome (LQTS) which can lead to sudden cardiac death. We previously showed that a reduction in extracellular K(+) concentration ([K(+)](o)) prolongs QT intervals in intact rabbits, and decreases the cell surface density of I(Kr) in rabbit ventricular myocytes and of the HERG channel expressed in human embryonic kidney (HEK) cells. OBJECTIVE: The goal of the present study was to gain insights into the mechanisms for low [K(+)](o) induced reduction in HERG expression levels. METHODS AND RESULTS: Using patch clamp, Western blot and confocal imaging methods, we demonstrated that at low [K(+)](o), the HERG channel entered a novel nonconducting state. Furthermore, this novel functional state triggered rapid internalization and degradation of the cell surface HERG channels. Thus, our data demonstrated for the first time a direct link between a gating state and the plasma membrane stability of an ion channel, HERG. Using HERG-permeant cations and site-directed mutagenesis, we identified the sites in the channel which are involved in the K(+)(o) dependence of HERG channels. CONCLUSIONS: Extracellular K(+) is a prerequisite for HERG function and membrane stability.
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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) | 0.000 | 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".