The rectification of heterotypic Cx46/Cx50 gap junction channels depends on intracellular magnesium
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Bibliographic record
Abstract
Gap junction (GJ) intercellular communication is crucial in many physiological and pathological processes. A GJ channel is formed by head-to-head docking of two hexameric hemichannels from two neighboring cells. Heterotypic GJ channels formed by two different homomeric connexin hemichannels often display rectification properties in the current–voltage relationship while the underlying mechanisms are not fully clear. Here we studied heterotypic Cx46/Cx50 GJs at a single GJ channel level. Our data showed unitary Cx46/Cx50 GJ channel conductance (γ<sub>j</sub>) rectification when 5 mmol/L Mg<sup>2+</sup> was included in the patch pipette solution, while no γ<sub>j</sub> rectification was observed when no Mg<sup>2+</sup> was added. Including 5 mmol/L Mg<sup>2+</sup> in pipette solution significantly decreased the γ<sub>j</sub> of homotypic Cx46 GJ with little change in homotypic Cx50 γ<sub>j</sub>. A missense point variant in Cx46 (E43F) reduced the Mg<sup>2+</sup>-dependent reduction in γ<sub>j</sub> of Cx46 E43F GJ, indicating that E43 might be partially responsible for Mg<sup>2+</sup>-dependent decrease in γ<sub>j</sub> of Cx46. A comprehensive understanding of Mg<sup>2+</sup> modulation of GJ at the individual channel level is useful in understanding factors in modulating GJ-mediated intercellular communication in health and diseases.
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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 it