Hydrogen peroxide and phosphoinositide metabolites synergistically regulate a cation current to influence neuroendocrine cell bursting
Bibliographic record
Abstract
Abstract In various neurons, including neuroendocrine cells, non‐selective cation channels elicit plateau potentials and persistent firing. Reproduction in the marine snail Aplysia californica is initiated when the neuroendocrine bag cell neurons undergo an afterdischarge, that is, a prolonged period of enhanced excitability and spiking during which egg‐laying hormone is released into the blood. The afterdischarge is associated with both the production of hydrogen peroxide (H2O2) and activation of phospholipase C (PLC), which hydrolyses phosphatidylinositol‐4,5‐bisphosphate into diacylglycerol (DAG) and inositol trisphosphate (IP3). We previously demonstrated that H2O2 gates a voltage‐dependent cation current and evokes spiking in bag cell neurons. The present study tests if DAG and IP3 impact the H2O2‐induced current and excitability. In whole‐cell voltage‐clamped cultured bag cell neurons, bath‐application of 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG), a DAG analogue, enhanced the H2O2‐induced current, which was amplified by the inclusion of IP3 in the pipette. A similar outcome was produced by the PLC activator, N‐(3‐trifluoromethylphenyl)‐2,4,6‐trimethylbenzenesulfonamide. In current‐clamp, OAG or OAG plus IP3, elevated the frequency of H2O2‐induced bursting. PKC is also triggered during the afterdischarge; when PKC was stimulated with phorbol 12‐myristate 13‐acetate, it caused a voltage‐dependent inward current with a reversal potential similar to the H2O2‐induced current. Furthermore, PKC activation followed by H2O2 reduced the onset latency and increased the duration of action potential firing. Finally, inhibiting nicotinamide adenine dinucleotide phosphate oxidase with 3‐benzyl‐7‐(2‐benzoxazolyl)thio‐1,2,3‐triazolo[4,5‐d]pyrimidine diminished evoked bursting in isolated bag cell neuron clusters. These results suggest that reactive oxygen species and phosphoinostide metabolites may synergize and contribute to reproductive behaviour by promoting neuroendocrine cell firing. image Key points Aplysia bag cell neurons secrete reproductive hormone during a lengthy burst of action potentials, known as the afterdischarge. During the afterdischarge, phospholipase C (PLC) hydrolyses phosphatidylinositol‐4,5‐bisphosphate into diacylglycerol (DAG) and inositol trisphosphate (IP3). Subsequent activation of protein kinase C (PKC) leads to H2O2 production. H2O2 evokes a voltage‐dependent inward current and action potential firing. Both a DAG analogue, 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG), and IP3 enhance the H2O2‐induced current, which is mimicked by the PLC activator, N‐(3‐trifluoromethylphenyl)‐2,4,6‐trimethylbenzenesulfonamide. The frequency of H2O2‐evoked afterdischarge‐like bursting is augmented by OAG or OAG plus IP3. Stimulating PKC with phorbol 12‐myristate 13‐acetate shortens the latency and increases the duration of H2O2‐induced bursts. The nicotinamide adenine dinucleotide phosphate oxidase inhibitor, 3‐benzyl‐7‐(2‐benzoxazolyl)thio‐1,2,3‐triazolo[4,5‐d]pyrimidine, attenuates burst firing in bag cell neuron clusters.
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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) | 0.002 | 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".