TRPA1 is necessary for IL-1β induced vagus nerve activity
Kristen Sparrow • October 02, 2021
This is an abstract from the recent Bioelectronic summit. I am keeping tabs on all of the cytokines and mechanisms because they, in many instances, can explain how acupuncture works. I realize this is can seem abstract, but with enough data coming in, we will have a fuller picture. Building the science brick by bridk.
P.14 TRPA1 is necessary for IL-1β induced vagus nerve activity
Harold A. Silverman, PhD1, Eric Chang, PhD1, Manojkumar Gunasekaran, PhD1, Tea Tsaava, MD1, Meghan Addorisio, BA,1, Tomas S. Huerta, BS1,2, Andrew Stiegler, BS1,2, Adam M. Kressel, MD, PhD1,3,4, Jian Hua Li, MS1, Qing Chang, PhD1, Qiong Zeng, PhD1, Adrian Chen1, Valentin A. Pavlov, PhD1,2,3,5, Ulf Andersson, MD, PhD5, Kevin J. Tracey, MD1,2,4,5,, Sangeeta S. Chavan, PhD1,2,4,5
1Laboratory for Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, US; 2Donald and Barbra Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York, US; 3Department of Surgery, Northshore University Hospital, Northwell Health, Manhasset, New York, US; 4The Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, New York, US; 5Department of Women’s and Children’s Health, Karolinska Institute, Karolinska University Hospital, Stockholm, SE
Correspondence: Kevin J. Tracey; Sangeeta S. Chavan
Sensory vagus nerve fibers transmit information in the form of action potentials to the central nervous system to maintain immunological homeostasis. Pro-inflammatory molecules including LPS, TNF, and IL-1β induce cytokine specific electrophysiological changes in vagus nerve signaling. In addition, these pro-inflammatory molecules directly activate nodose ganglion neurons, the location of sensory vagus nerve cell bodies. Previous studies have shown cytokines have a direct impact on cation channels TRPV1 and TRPA1, which are expressed on sensory fibers of the vagus nerve. Reasoning that these cation channels may play a role in vagus nerve mediated cytokine signaling we explored TRPA1’s role in IL-1β induced vagus nerve activity. Extra neural electrical activity was recorded from the cervical vagus nerve in response to i.p. administration of IL-1β. IL-1β induces a significant increase in vagus nerve activity in wild type mice, however this response was ablated in whole body TRPA1 KO mice as well as neuronal specific TRPA1 KO mice (SynCre-TRPA1flox). Using calcium imaging and whole cell patch clamp recordings, we observed nodose ganglion neurons deficient in TRPA1 do not respond to IL-1β application. In addition, IL-1β induced calcium influx was inhibited by administration of the TRPA1 antagonist AM0902. These results elucidate a novel role for the TRPA1 cation channel as a necessary component for IL-1β induced vagus nerve signaling.
