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 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".