Temperature and redox state dependence of native Kv2.1 currents in rat pancreatic β‐cells
Bibliographic record
Abstract
In pancreatic beta-cells, voltage-dependent K(+) (Kv) channels repolarise glucose-stimulated action potentials. Kv channels are therefore negative regulators of Ca(2+) entry and insulin secretion. We have recently demonstrated that Kv2.1 mediates the majority of beta-cell voltage-dependent outward K(+) current and now investigate the function of native beta-cell Kv2.1 channels at near-physiological temperatures (32-35 degrees C). While beta-cell voltage-dependent outward K(+) currents inactivated little at room temperature, both fast-inactivation (111.5 +/- 14.3 ms) and slow-inactivation (1.21 +/- 0.12 s) was observed at 32-35 degrees C. Kv2.1 mediates the fast-inactivating current observed at 32-35 degrees C, since it could be selectively ablated by expression of a dominant-negative Kv2.1 construct (Kv2.1N). The surprising ability of Kv2.1N to selectively remove the fast-inactivating component, together with its sensitivity to tetraethylammonium (TEA), demonstrate that this component is not mediated by the classically fast-inactivating and TEA-resistant channels such as Kv1.4 and 4.2. Increasing the intracellular redox state by elevating the cytosolic NADPH/NADP(+) ratio from 1/10 to 10/1 increased the rates of both fast- and slow-inactivation. In addition, increasing the intracellular redox state also increased the relative contribution of the fast-inactivation component from 38.8 +/- 2.1 % to 55.9 +/- 1.8 %. The present study suggests that, in beta-cells, Kv2.1 channels mediate a fast-inactivating K(+) current at physiological temperatures and may be regulated by the metabolic generation of NADPH.
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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".