Enhancement of the large conductance, Ca <sup>2+</sup> ‐activated K <sup>+</sup> (BK) channel current by cGMP‐dependent protein kinase requires multiple phosphorylation sites on the C‐terminal tail
Bibliographic record
Abstract
Nitric oxide (NO)‐mediated activation of the cGMP‐dependent protein kinase (cGK) leads to relaxation of vascular smooth muscle (VSM) through a process involving phosphorylation of the BK channel. In VSM cells, this modification increases channel open probability, resulting in membrane hyperpolarization and closure of voltage‐gated Ca 2+ channels. Although this paradigm is now generally accepted, the target residues of cGK‐mediated phosphorylation on the BK channel have thus far been inadequately characterized at the molecular level. We have scrutinized this BK channel phosphorylation by identifying several putative phosphorylation sites on the C‐terminus via electrophysiological and biochemical assays. Wild type (WT) and Ser to Ala mutated BK channels were expressed in cultured rat aortic VSM cells (A7r5) and studied using the cell‐attached patch clamp technique. The NO donor spermine NONOate (5 μM) and the membrane‐permeant analogue db‐cGMP (0.1 mM) enhanced WT BK channel activity, while several BK channel mutants had diminished responses to either stimulant. Exposure to the Ca 2+ ionophore A23187 enhanced channel activity in both WT and mutant channels. These results demonstrate that BK current enhancement by NO/cGK‐mediated phosphorylation requires multiple sites on the C‐terminus tail, in an apparent all‐or‐none fashion. Supported by NSERC (APB) and a Kertland Family Scholarship (BDK).
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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".