Low voltage‐activated calcium channels gate transmitter release at the dorsal root ganglion sandwich synapse
Bibliographic record
Abstract
Key points Sensory neurons in dorsal root ganglia (DRG) lack direct inter‐somatic synaptic contacts but a subpopulation can communicate with their immediate neighbours via transglial, neuron–glial cell–neuron ‘sandwich synapses’. We used gently dissociated chick DRG to explore the properties and identity of the voltage sensitive calcium channel responsible for gating transmitter (ATP) release at the neuron‐to‐glial cell synapse. A combined pharmacological and biophysical characterization identified the T type, CaV3.2 calcium channel. The low voltage‐activated and inactivation‐sensitive properties of CaV3.2 suggest that sandwich synapse transmission is gated not only by action potentials but also by sub‐threshold membrane depolarizations. CaV3.2 modulating agents are of interest as anaesthetics, raising the possibility that sandwich synapse transmission plays a role in the aetiology of DRG‐derived abnormal sensation and pain. Abstract A subpopulation of dorsal root ganglion (DRG) neurons are intimately attached in pairs and separated solely by thin satellite glial cell membrane septa. Stimulation of one neuron leads to transglial activation of its pair by a bi‐, purinergic/glutamatergic synaptic pathway, a transmission mechanism that we term sandwich synapse (SS) transmission. Release of ATP from the stimulated neuron can be attributed to a classical mechanism involving Ca 2+ entry via voltage‐gated calcium channels (CaV) but via an unknown channel type. Specific blockers and toxins ruled out CaV1, 2.1 and 2.2. Transmission was, however, blocked by a moderate depolarization (−50 mV) or low‐concentration Ni 2+ (0.1 m m ). Transmission persisted using a voltage pulse to −40 mV from a holding potential of −80 mV, confirming the involvement of a low voltage‐activated channel type and limiting the candidate channel type to either CaV3.2 or a subpopulation of inactivation‐ and Ni 2+ ‐sensitive CaV2.3 channels. Resistance of the neuron calcium current and SS transmission to SNX482 argue against the latter. Hence, we conclude that inter‐somatic transmission at the DRG SS is gated by CaV3.2 type calcium channels. The use of CaV3 family channels to gate transmission has important implications for the biological function of the DRG SS as information transfer would be predicted to occur not only in response to action potentials but also to sub‐threshold membrane voltage oscillations. Thus, the SS synapse may serve as a homeostatic signalling mechanism between select neurons in the DRG and could play a role in abnormal sensation such as neuropathic pain.
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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 | 0.001 |
| 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".