Caloxin 1c2‐ A Novel Engineered Selective Inhibitor of Plasma Membrane Ca <sup>2+</sup> ‐ Pump Isoform 4, Effects on Coronary Artery
Bibliographic record
Abstract
Coronary artery smooth muscle expresses two isoforms of plasma membrane Ca 2+ pumps: PMCA4 and PMCA1. The previously reported peptide inhibitor caloxin 1b1 was obtained by using extracellular domain 1 (amino acids 115–131) of PMCA4 as the target. Here, we report its mutagenesis by creating a phage display library of caloxin 1b1‐like peptides. The library was screened by affinity chromatography with the PMCA purified from the human erythrocyte ghosts that contain mainly PMCA4 isoform. This yielded caloxin 1c2 with the following key properties: a) Ki = 2.3 ± 0.3 μM which corresponds to a 20x higher affinity for PMCA than caloxin 1b1, and b) it is isoform selective since it has 10x higher affinity for PMCA4 than for PMCA1, 2 or 3. It had the following functional effects on the coronary artery smooth muscle: a) it increased the basal tone of the de‐endothelialized arteries: the increase being similar at 10, 20 or 50 μM, and b) it enhanced the increase in the force of contraction at 0.05 but not at 1.6 mM extracellular Ca 2+ when Ca 2+ ‐extrusion via the Na + ‐Ca 2+ ‐exchanger and the sarco/endoplasmic reticulum Ca 2+ pump were inhibited. We conclude that PMCA4 is pivotal to Ca 2+ homeostasis in coronary artery smooth muscle. We anticipate caloxin 1c2 to aid in understanding the role of PMCA4 in signal transduction and Ca 2+ homeostasis due to its isoform selectivity and ability to act when added extracellularly. Supported by Heart & Stroke Foundation of Ontario.
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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".