Activation of TRPA1 and TRPM3 triggers Ca 2+ waves in central terminals of sensory neurons and facilitates synaptic activity in the spinal dorsal horn

Yaroslav E Andrianov; Alex L Keyes; Charles A Warwick; Miriam C McDonough; Leonid P Shutov; Kavita S Solanki; Jon M Resch; Alexander G Bassuk; Nana Voitenko; Pavel Belan; Yuriy M Usachev

doi:10.1113/JP286407

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Activation of TRPA1 and TRPM3 triggers Ca 2+ waves in central terminals of sensory neurons and facilitates synaptic activity in the spinal dorsal horn

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Activation of TRPA1 and TRPM3 triggers Ca 2+ waves in central terminals of sensory neurons and facilitates synaptic activity in the spinal dorsal horn

Yaroslav E Andrianov, Alex L Keyes, Charles A Warwick, Miriam C McDonough, Leonid P Shutov, Kavita S Solanki, Jon M Resch, Alexander G Bassuk, Nana Voitenko, Pavel Belan, …

The Journal of physiology, Vol.603(20), pp.6365-6389

10/2025

DOI: 10.1113/JP286407

PMCID: PMC12559988

PMID: 40172079

Appears in UI Libraries Support Open Access

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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+ signalling at spinal synapses. However, information about TRPA1- and TRPM3-induced Ca2+ signalling in the dorsal horn (DH) of the spinal cord is lacking. Here, we describe a dual-colour 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.

sensory synapse

TRPA1

dorsal horn

Ca2+ imaging

TRPV1

spinal cord

TRPM3

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Details

Title: Subtitle: Activation of TRPA1 and TRPM3 triggers Ca 2+ waves in central terminals of sensory neurons and facilitates synaptic activity in the spinal dorsal horn
Creators: Yaroslav E Andrianov - Department of Neuroscience & Pharmacology and The Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Alex L Keyes - University of Iowa
Charles A Warwick - University of Pittsburgh
Miriam C McDonough - University of Iowa
Leonid P Shutov - University of Iowa
Kavita S Solanki - University of Iowa
Jon M Resch - Department of Neuroscience & Pharmacology and The Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Alexander G Bassuk - Departments of Pediatrics and Neurology, The Iowa Neuroscience Institute and the Hawkeye Intellectual and Developmental Disabilities Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Nana Voitenko - Dobrobut Academy Medical School, Kyiv, Ukraine
Pavel Belan - Bogomoletz Institute of Physiology
Yuriy M Usachev - Department of Neuroscience & Pharmacology and The Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: The Journal of physiology, Vol.603(20), pp.6365-6389
DOI: 10.1113/JP286407
PMID: 40172079
PMCID: PMC12559988
NLM abbreviation: J Physiol
ISSN: 0022-3751
eISSN: 1469-7793
Publisher: Wiley
Grant note: T32 DK112751 / NIDDK NIH HHS R01 NS127428 / NINDS NIH HHS R01NS125884 / NINDS NIH HHS R01 NS113189 / NINDS NIH HHS
Language: English
Electronic publication date: 04/02/2025
Date published: 10/2025
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: 9984805011202771

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