Asset Details
Do you wish to reserve the book?
Prostaglandin E2 depolarises sensory axons in vitro in an ANO1 and Nav1.8 dependent manner
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Prostaglandin E2 depolarises sensory axons in vitro in an ANO1 and Nav1.8 dependent manner
Do you wish to request the book?
Prostaglandin E2 depolarises sensory axons in vitro in an ANO1 and Nav1.8 dependent manner
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Prostaglandin E2 depolarises sensory axons in vitro in an ANO1 and Nav1.8 dependent manner
2024
Overview
Prostaglandin E2 (PGE2) is a major contributor to inflammatory pain hyperalgesia, however, the extent to which it modulates the activity of nociceptive axons is incompletely understood. We developed and characterized a microfluidic cell culture model to investigate sensitisation of the axons of dorsal root ganglia neurons. We show that application of PGE2 to fluidically isolated axons leads to sensitisation of their responses to depolarising stimuli. Interestingly the application of PGE2 to the DRG axons elicited a direct and persistent spiking activity propagated to the soma. Both the persistent activity and the membrane depolarisation in the axons are abolished by the EP4 receptor inhibitor and a blocker of cAMP synthesis. Further investigated into the mechanisms of the spiking activity showed that the PGE2 evoked depolarisation was inhibited by Nav1.8 sodium channel blockers but was refractory to the application of TTX or zatebradine. Interestingly, the depolarisation of axons was blocked by blocking ANO1 channels with T16Ainh-A01. We further show that PGE2-elicited axonal responses are altered by the changes in chloride gradient within the axons following treatment with bumetanide a Na-K-2Cl cotransporter NKCC1 inhibitor, but not by VU01240551 an inhibitor of potassium-chloride transporter KCC2. Our data demonstrate a novel role for PGE2/EP4/cAMP pathway which culminates in a sustained depolarisation of sensory axons mediated by a chloride current through ANO1 channels. Therefore, using a microfluidic culture model, we provide evidence for a potential dual function of PGE2 in inflammatory pain: it sensitises depolarisation-evoked responses in nociceptive axons and directly triggers action potentials by activating ANO1 and Nav1.8 channels.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Action Potentials - drug effects
/ Animals
/ Axons
/ Chloride
/ Ganglia, Spinal - drug effects
/ Ganglia, Spinal - metabolism
/ Humanities and Social Sciences
/ NAV1.8 Voltage-Gated Sodium Channel - metabolism
/ Pain
/ Potassium-chloride cotransporter
/ Rats
/ Receptors, Prostaglandin E, EP4 Subtype - metabolism
/ Science
/ Sensory Receptor Cells - drug effects
/ Sensory Receptor Cells - metabolism
/ Sodium
