TY - JOUR
T1 - The transient receptor potential channel TRPA1
T2 - From gene to pathophysiology
AU - Nilius, Bernd
AU - Appendino, Giovanni
AU - Owsianik, Grzegorz
N1 - Funding Information:
We thank the members of the Laboratory of Ion Channel Research for helpful discussions. This work was supported by grants from the Belgian Federal Government (IUAP P5/05), the Research Foundation-Flanders (G.0172.03, G.0565.07 and G.0149.03), and the Research Council of the KU Leuven (GOA 2004/07 and EF/95/010).
PY - 2012/11
Y1 - 2012/11
N2 - The Transient Receptor Potential Ankyrin 1 channel (TRPA1), is a member of the large TRP family of ion channels, and functions as a Ca2+ permeable non-selective cation channel in many different cell processes, ranging from sensory to homeostatic tasks. TRPA1 is highly conserved across the animal kingdom. The only mammalian TRPA subfamily member, TRPA1, is widely expressed in neuronal (e.g. sensory dorsal root and trigeminal ganglia neurons)- and in non-neuronal cells (e.g. epithelial cells, hair cells). It exhibits 14-19 amino-(N-)terminal ankyrin repeats, an unusual structural feature. The TRPA1 channel is activated by noxious cold (<17 °C) as well as by a plethora of chemical compounds that includes not only electrophilic compounds and oxidants that can modify, in an alkylative or oxidative fashion, nucleophilic cysteine residues in the channel's N-terminus, but also compounds that do not covalently bind to the channel proteins (e.g. menthol, nifedipin). Based on localization and functional properties, TRPA1 is considered a key player in acute and chronic (neuropathic) pain and inflammation. Moreover, its role in the (patho)physiology of nearly all organ systems is anticipated, and will be discussed along with the potential of TRPA1 as a drug target for the management of various pathological conditions.
AB - The Transient Receptor Potential Ankyrin 1 channel (TRPA1), is a member of the large TRP family of ion channels, and functions as a Ca2+ permeable non-selective cation channel in many different cell processes, ranging from sensory to homeostatic tasks. TRPA1 is highly conserved across the animal kingdom. The only mammalian TRPA subfamily member, TRPA1, is widely expressed in neuronal (e.g. sensory dorsal root and trigeminal ganglia neurons)- and in non-neuronal cells (e.g. epithelial cells, hair cells). It exhibits 14-19 amino-(N-)terminal ankyrin repeats, an unusual structural feature. The TRPA1 channel is activated by noxious cold (<17 °C) as well as by a plethora of chemical compounds that includes not only electrophilic compounds and oxidants that can modify, in an alkylative or oxidative fashion, nucleophilic cysteine residues in the channel's N-terminus, but also compounds that do not covalently bind to the channel proteins (e.g. menthol, nifedipin). Based on localization and functional properties, TRPA1 is considered a key player in acute and chronic (neuropathic) pain and inflammation. Moreover, its role in the (patho)physiology of nearly all organ systems is anticipated, and will be discussed along with the potential of TRPA1 as a drug target for the management of various pathological conditions.
KW - Ankyrin repeat domain
KW - Ca channels
KW - Channeloparthies
KW - Mechano-sensing
KW - Nociception
KW - Transient receptor potential
UR - http://www.scopus.com/inward/record.url?scp=84867872657&partnerID=8YFLogxK
U2 - 10.1007/s00424-012-1158-z
DO - 10.1007/s00424-012-1158-z
M3 - Review article
SN - 0031-6768
VL - 464
SP - 425
EP - 458
JO - Pflugers Archiv European Journal of Physiology
JF - Pflugers Archiv European Journal of Physiology
IS - 5
ER -