Abstract
92 - Activation of TRPA1 and TRPM3 Triggers Ca2+ Waves in Central Terminals of Sensory Neurons and Facilitates Synaptic Activity in the Spinal Dorsal Horn
The journal of pain, Vol.29(Supplement), 104888
04/2025
DOI: 10.1016/j.jpain.2025.104888
Abstract
Transient receptor potential ankyrin 1 (TRPA1) and melastatin 3 (TRPM3) are transduction channels of sensory neurons that play major roles in peripheral mechanisms of somatosensation, including thermosensation, chemosensation and nociception. Recent studies suggest that both channels also contribute to central mechanisms of pain processing at the spinal cord level. TRPA1 and TRPM3 are highly permeable for Ca2+ suggesting that they could regulate Ca2+ signaling at spinal synapses. However, information about TRPA1- and TRPM3-induced Ca2+ signaling in the dorsal horn (DH) of the spinal cord is lacking. Here, we describe a dual-color technique for simultaneously measuring Ca2+ concentration ([Ca2+]i) in central terminals of sensory neurons and in spinal DH neurons by green (GCaMP3) and red (jRGECO1a) Ca2+ indicators, using two-photon imaging in isolated mouse spinal cord with attached dorsal roots (DR). DR stimulation elicited [Ca2+]i transients in axonal boutons of primary afferents and in cell bodies of DH neurons. The antagonists of AMPA and NMDA glutamate receptors, CNQX and AP5, inhibited [Ca2+]i transients in DH neurons, but not in sensory axonal boutons. Selective agonists of TRPA1 and TRPM3, ASP7663 and CIM0216, induced complex [Ca2+]i responses in distinct but partially overlapping subsets of sensory axonal boutons. Concomitant [Ca2+]i elevations were observed in DH neurons, which were blocked by CNQX and AP5. Patch-clamp recordings from DH neurons showed that ASP7663 and CIM0216 markedly enhanced excitatory synaptic activity. In summary, our findings suggest that TRPA1 and TRPM3 on central terminals of sensory neurons regulate presynaptic [Ca2+]i and synaptic transmission in the spinal DH.
Details
- Title: Subtitle
- 92 - Activation of TRPA1 and TRPM3 Triggers Ca2+ Waves in Central Terminals of Sensory Neurons and Facilitates Synaptic Activity in the Spinal Dorsal Horn
- Creators
- Alex KeyesYaroslav AndrianovCharles WarwickLeonid ShutovAlexander BassukNana VoitenkoPavel BelanYuriy Usachev
- Resource Type
- Abstract
- Publication Details
- The journal of pain, Vol.29(Supplement), 104888
- DOI
- 10.1016/j.jpain.2025.104888
- ISSN
- 1526-5900
- eISSN
- 1528-8447
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 04/2025
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Anesthesia; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Neurology (Pediatrics)
- Record Identifier
- 9984820566402771
Metrics
12 Record Views