Perturbation of synaptic vesicle delivery during neurotransmitter release triggered independently of calcium influx
Bibliographic record
Abstract
Although much evidence suggests that calcium (Ca(2+)) usually triggers synaptic vesicle exocytosis and neurotransmitter release, the role of Ca(2+) in vesicle endocytosis and in the delivery of fusion-competent vesicles (i.e. mobilisation and/or priming) in nerve terminals remains unclear. To address this issue, we have studied synaptic vesicle dynamics in cultured rat neurones under conditions where neurotransmitter release is triggered independently of Ca(2+) using the secretagogue Ruthenium Red (RR). Using a prolonged stimulation protocol, we find that RR causes a rapid increase in neurotransmitter release followed by a gradually decrementing response. In contrast, when release is triggered by moderate membrane depolarisation caused by saline containing 18 mM K(+), release is sustained. These observations suggest that when release is triggered independently of a rise in Ca(2+), endocytosis or vesicle mobilisation/priming are perturbed. Using FM2-10, a fluorescent indicator of synaptic vesicle cycling, we find that neurotransmitter release triggered by RR is accompanied by both uptake and release of this dye, thereby suggesting that vesicle endocytosis is not blocked. To evaluate whether synaptic vesicle mobilisation/priming is perturbed in the absence of a rise in Ca(2+), we compared the kinetics of FM2-10 loss during prolonged stimulation. While 18 mM K(+) induced gradual and continuous dye loss, RR only induced substantial dye loss during the first minute of stimulation. In the presence of low concentrations of the Ca(2+) ionophore ionomycin, release caused by RR was prolonged. Taken together, these results provide evidence suggesting that, although a rise in intraterminal Ca(2+) is not required for endocytosis, it is essential for the continuous delivery of fusion-competent vesicles and to maintain neurotransmitter release during prolonged stimulation.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".