Differences in phosphorylation‐mediated K+ channel regulation between vascular smooth muscle cells from cremaster and cerebral resistance vessels
Bibliographic record
Abstract
The activity of maxi K+ channels (BKCa) differs in vascular smooth muscle cells (VSMC) from cremaster muscle (CM) and cerebral (CER) resistance arteries. As BKCa are regulated by cyclic nucleotide‐dependent phosphorylation, we examined channel responses to the cAMP stimulant forskolin, dependence on PKA and PKG, and differences in basal phoshorylation levels. Isolated VSMCs were studied using whole cell patch clamp. Forskolin (10– 30 μM) increased whole cell K+ current in both preparations, increasing current at +70 mV by 170.2 ± 1.2 % in CER VSMCs and 136.1 ± 2.5 % in CM VSMCs. Forskolin‐induced K+ currents showed weak sensitivity to the PKA blocker, KT5720 (0.3 μM), while being abolished by the PKG inhibitor, KT5823 (0.3 μM). Basal phosphorylation was apparent as KT5823 reduced basal K+ current and STOCs in both cell preparations. To further determine contributions from basal phoshorylation, VSMCs were dialyzed with alkaline phosphatase (AP; 350U/ml) via the patch pipette. AP reduced K+ current at +70 mV by 49.3 ± 0.9 % in CER VSMCs compared to 28.6 ± 2.1 % in VSMCs from CM and prevented a further reduction in current by KT5823. The data suggest that K+ conductance can be modulated by cAMP in both preparations by mechanisms involving cross‐talk to PKG. Further, BKCa in CER VSMCs may exhibit a higher level of basal phosphorylation, which contributes to their higher basal activity relative to VSMCs from CM. (Supp NIH HL092241)
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".