A subthreshold persistent sodium current mediates bursting in rat subfornical organ neurones
Bibliographic record
Abstract
It is widely accepted that while release of amino acid neurotransmitters occurs with relatively high fidelity, peptidergic synapses require clustered bursts of action potentials for optimal transmitter release. Here we describe for the first time the occurrence and mechanisms of bursting by neurones in the subfornical organ (SFO), cells that utilize the peptide angiotensin II (ANG) in neurotransmission in autonomic pathways. In current clamp recording of isolated SFO neurones in vitro, 53 % (n = 74) showed either spontaneous or evoked burst-like discharge patterns. Bursts typically appeared as shifts in bistable membrane potential, with action potentials superimposed on a depolarizing afterpotential (DAP). Similarly, in vivo single unit recordings of identified SFO neurones showed that 9 of 15 neurones fired in bursts. The pattern of bursting, as well as duration of evoked DAPs was strongly dependent upon membrane potential, suggesting that the DAP contributes to burst generation. Based on our previous observation of calcium-sensing receptor (CaR)-activated bursts, we investigated the effects of NPS R-467, an allosteric agonist of the CaR, on evoked DAPs. NPS R-467 (1 microM) potentiated DAP duration throughout the voltage range tested. We observed a dependence of evoked DAPs upon Na+ channels, as shown by sensitivity to tetrodotoxin (0.5 microM) or reduction of external [Na+] from 140 to 40 mM. The duration of DAPs suggested that a persistent Na+ current mediates these events. Voltage-clamp analysis revealed the presence of a subthreshold sodium current, INaP. Pharmacological blockade of INaP with 100 microM lidocaine reduced the duration of evoked DAPs, and inhibited bursting in SFO neurones. Facilitation of INaP with 10 nM anemone toxin (ATX) increased DAP duration and led to marked excitation of bursting cells. These data indicate that INaP is the main current underlying bursting in SFO neurones. Our observations of receptor-mediated facilitation of bursting by SFO neurones represents an intriguing mechanism through which the release of the peptide neurotransmitter ANG may be regulated.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".