Promiscuous and Reversible Blocker of Presynaptic Calcium Channels in Frog and Crayfish Neuromuscular Junctions From<i>Phoneutria nigriventer</i>Spider Venom
Bibliographic record
Abstract
Peptide channel blockers found in venoms of many predators are useful pharmacological tools and potential therapeutic agents. The venom of the Brazilian spider Phoneutria nigriventer contains a fraction, omega-phonetoxin-IIA (omega-Ptx-IIA, 8360 MW), which blocks Ca2+ channels. At frog neuromuscular junctions (NMJ) bathed in normal Ca2+ (1.8 mM) saline, omega-Ptx IIA did not affect spontaneous transmitter release but reversibly reduced evoked transmitter release by 75 and 95% at 12 and 24 nM, respectively. In contrast, toxin effects were irreversible in low-Ca2+ (0.5 mM) saline. Ca2+ imaging in normal-Ca2+ saline showed that omega-Ptx-IIA partially blocked stimulus-dependent presynaptic Ca2+ signals, and the blockade was almost completely reversible. Increases in spontaneous release frequency induced by high extracellular K+ were blocked by omega-Ptx-IIA. Therefore omega-Ptx-IIA blocks N-type Ca2+ channels, which admit Ca2+ that triggers transmitter release at the frog NMJ. Additional evidence predicts that omega-Ptx-IIA binds to N-type Ca2+ channels at a different site from that of omega-Conotoxin-GVIA. omega-Ptx-IIA also gave a low-affinity partial blockade of transmitter release and presynaptic Ca2+ signals at crayfish NMJs where P-type channels are blocked by omega-agatoxin-IVA. The Ca2+-dependent reversibility and promiscuity of this toxin may make it highly useful experimentally and therapeutically.
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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".