Presynaptic organization of CaV2 channels with specific vesicle pools in SCG vs rat tail artery
Bibliographic record
Abstract
Peripheral sympathetic nerves co‐release multiple neurotransmitters to modulate the activity of their target organ, for example mediating physiological regulation of cardiac contractility and systemic vascular tone. However, the release of “co‐released” transmitters like norepinephrine (NE) and ATP can be differentially regulated, for example by relying on specific isoforms of voltage‐gated Ca2+ channels (CaV), and we previously reported that NE‐ and ATP‐containing vesicles segregate in pools that preferentially co‐localize with specific CaV2 isoforms in rat tail artery. Whether this observation generalizes to other sympathetic nerves is not known, but it is of fundamental importance to understanding the molecular biology of sympathetic co‐release. OBJECTIVE To determine whether specific isoforms of CaV selectively associate with pools of vesicles enriched with transporters for NE or ATP in multiple peripheral sympathetic nerves. METHODS We performed epifluorescence imaging of intact rat tail artery and cultured superior cervical ganglia (SCG) neurons, comparing the localization and intensity correlation of CaV2.1, CaV2.2, and CaV2.3 with vesicle markers for NE (VMAT2) and ATP (VNUT/SlC17A) containing vesicles or suitable surrogate markers. RESULTS We confirmed that VMAT2 and VNUT are often but not always found in the same varicosities. While VMAT2 is broadly distributed in varicosity, VNUT localizes as discrete puncta at the perimeter of varicosity and does not co‐localize with synaptagmin1 in SCG neurons, similar rat artery nerves. CaV2.3 and CaV2.1, like VNUT, localize to the periphery of the varicosities, while CaV2.2 more closely mimics to the distribution of VMAT2. These findings mirror our observations in rat tail artery, in which NE release is most sensitive to CaV2.2 inhibition and ATP‐mediated contraction is blocked by CaV2.3 inhibition. CONCLUSION We show that synaptic organization of CaV2 isoforms with specific pools of vesicle in a cultured nerve system closely recapitulates that found in vivo. This observation further validates cultured SCG neurons as an experimentally tractable and physiologically revenant model to study presynaptic cell biology relevant to the regulation of both cardiac output and vasoregulation. Support or Funding Information 1. Natural Sciences and Engineering Research Council of Canada.2. Canadian Foundation for Innovation
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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".