State‐dependent barium block of wild‐type and inactivation‐deficient HERG channels in <i>Xenopus</i> oocytes
Bibliographic record
Abstract
The effects of Ba2+ on current resulting from the heterologous expression of the human ether-à-go-go related gene (HERG) (IHERG) was studied with two-electrode voltage clamp techniques in Xenopus oocytes. Ba2+ produced time- and voltage-dependent block of IHERG. Significant inhibition was seen at concentrations as low as 1 microM. Inhibition was greatest at step potentials between -40 and 0 mV; at more positive potentials, inhibition decreased in association with time-dependent unblocking of channels. An inactivation-attenuated mutant of HERG (S631A) was prepared and expressed in Xenopus oocytes. Ba2+ block of S631A differed from that of HERG in that extensive unblocking was no longer seen at positive potentials and the voltage dependence of step current block was greatly attenuated. A mathematical model was applied to analyse quantitatively the inhibitory effects of Ba2+ on IHERG. The model suggested similar voltage-dependent affinity of Ba2+ for the open and closed states, along with absence of binding to the inactivated state, and accounted well for Ba2+ effects on both wild-type and S631A channels. We conclude that Ba2+ potently inhibits IHERG in a characteristic state-dependent fashion, with strong unblocking at positive potentials related to the presence of an intact C-type inactivation mechanism.
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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 | 0.001 |
| 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".