Localization of TRPA1 channels and characterization of TRPA1 mediated responses in dural and pial arteries in vivo after intracarotid infusion of Na2S

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

BACKGROUND: The Transient Receptor Potential Ankyrin 1 (TRPA1) channel might play a role in migraine. However, different mechanisms for this have been suggested. The purpose of our study was to investigate the localization and significance of TRPA1 channels in rat pial and dural arteries.

METHODS: Immunofluorescence microscopy was used to localize TRPA1 channels in dural arteries, pial arteries, dura mater and trigeminal ganglion. The genuine closed cranial window model was used to examine the effect of Na2S, a donor of the TRPA1 channel opener H2S, on the diameter of pial and dural arteries. Further, we performed blocking experiments with TRPA1 antagonist HC-030031, calcitonin gene-related peptide (CGRP) receptor antagonist olcegepant and KCa3.1 channel blocker TRAM-34.

RESULTS: TRPA1 channels were localized to the endothelium of both dural and pial arteries and in nerve fibers in dura mater. Further, we found TRPA1 expression in the membrane of trigeminal ganglia neuronal cells, some of them also staining for CGRP. Na2S caused dilation of both dural and pial arteries. In dural arteries, this was inhibited by HC-030031 and olcegepant. In pial arteries, the dilation was inhibited by TRAM-34, suggesting involvement of the KCa3.1 channel.

CONCLUSION: Na2S causes a TRPA1- and CGRP-dependent dilation of dural arteries and a KCa3.1 channel-dependent dilation of pial arteries in rats.

OriginalsprogEngelsk
TidsskriftCephalalgia : an international journal of headache
Vol/bind40
Udgave nummer12
Sider (fra-til)1310-1320
Antal sider11
ISSN0333-1024
DOI
StatusUdgivet - 2020

ID: 244444870