Abstract
The TRPA1 ion channel is expressed in nociceptive (pain-sensitive) somatosensory neurons and is activated by a wide variety of chemical irritants, such as acrolein in smoke or isothiocyanates in mustard. Here, we investigate the enhancement of TRPA1 function caused by inflammatory mediators, which is thought to be important in lung conditions such as asthma and COPD. Protein kinase A is an important kinase acting downstream of inflammatory mediators to cause sensitization of TRPA1. By using site-directed mutagenesis, patch-clamp electrophysiology and calcium imaging we identify four amino acid residues, S86, S317, S428, and S972, as the principal targets of PKA-mediated phosphorylation and sensitization of TRPA1.
Highlights
The Transient Receptor Potential Ankyrin 1 (TRPA1) channel is expressed in nociceptive somatosensory neurons, and activation of the channel triggers a sensation of stinging pain [1,2,3,4]
Results hTRPA1 is acutely sensitized by activation of protein kinase A (PKA)
The gating of TRPV1 is rapidly and potently enhanced when PKA or protein kinase C (PKC) are activated by a variety of inflammatory mediators, and when TrkA is activated by the binding of Nerve growth factor (NGF)
Summary
The Transient Receptor Potential Ankyrin 1 (TRPA1) channel is expressed in nociceptive (pain-sensitive) somatosensory neurons, and activation of the channel triggers a sensation of stinging pain [1,2,3,4]. TRPA1 has been proposed to be activated by noxious cold [4,14,15] but this remains controversial [2,16]. Both intracellular and extracellular calcium can activate TRPA1 and potentiate its response to several agonists, followed by long lasting inactivation of the channel [2,16,17,18]. Immune and other cells release a range of inflammatory mediators, which modulate ion channels and thereby sensitize the responses of peripheral nociceptors. We PLOS ONE | DOI:10.1371/journal.pone.0170097 January 11, 2017
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
