Junctophilin Proteins Tether a Cav1-RyR2-KCa3.1 Tripartite Complex to Regulate Neuronal Excitability
Bibliographic record
Abstract
The excitability of CA1 hippocampal pyramidal cells is mediated by a slow AHP (sAHP) that responds to calcium increases by Cav1 calcium channels and ryanodine receptors (RyR). We used super-resolution and FRET microscopy to investigate the proximity and functional coupling among Cav1.3/Cav1.2, RyR2, and KCa3.1 potassium channels that contribute to the sAHP. dSTORM and FRET imaging shows that Cav1.3, RyR2, and KCa3.1 are organized as a triprotein complex that colocalizes with junctophilin (JPH) 3 and 4 proteins that tether the plasma membrane to the endoplasmic reticulum. JPH3 and JPH4 shRNAs dissociated a Cav1.3-RyR2-KCa3.1 complex and reduced the IsAHP. Infusing JPH3 and JPH4 antibodies into CA1 cells reduced IsAHP and spike accommodation. These data indicate that JPH3 and JPH4 proteins maintain a Cav1-RyR2-KCa3.1 complex that allows two calcium sources to act in tandem to define the activation properties of KCa3.1 channels and the IsAHP.
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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) | 0.001 | 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 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".