TY - JOUR
T1 - Thimerosal decreases TRPV1 activity by oxidation of extracellular sulfhydryl residues
AU - Jin, Yunju
AU - Kim, Dong Kwan
AU - Khil, Lee Yong
AU - Oh, Uhtaek
AU - Kim, Jun
AU - Kwak, Jiyeon
N1 - Funding Information:
This work was supported by a grant (97-0403-13-01-5) from the Korean Science and Engineering Foundation.
PY - 2004/10/21
Y1 - 2004/10/21
N2 - TRPV1, a receptor for capsaicin, plays a key role in mediating thermal and inflammatory pain. Because the modulation of ion channels by the cellular redox state is a significant determinant of channel function, we investigated the effects of sulfhydryl modification on the activity of TRPV1. Thimerosal, which oxidizes sulfhydryls, blocked the capsaicin-activated inward current (I cap) in cultured sensory neurons, in a reversible and dose-dependent manner, which was prevented by the co-application of the reducing agent, dithiothreitol. Among the three cysteine residues of TRPV1 that are exposed to the extracellular space, the oxidation-induced effect of thimerosal on I cap was blocked only by a point mutation at Cys621. These results suggest that the modification of an extracellular thiol group can alter the activity of TRPV1. Consequently, we propose that such a modulation of the redox state might regulate the physiological activity of TRPV1.
AB - TRPV1, a receptor for capsaicin, plays a key role in mediating thermal and inflammatory pain. Because the modulation of ion channels by the cellular redox state is a significant determinant of channel function, we investigated the effects of sulfhydryl modification on the activity of TRPV1. Thimerosal, which oxidizes sulfhydryls, blocked the capsaicin-activated inward current (I cap) in cultured sensory neurons, in a reversible and dose-dependent manner, which was prevented by the co-application of the reducing agent, dithiothreitol. Among the three cysteine residues of TRPV1 that are exposed to the extracellular space, the oxidation-induced effect of thimerosal on I cap was blocked only by a point mutation at Cys621. These results suggest that the modification of an extracellular thiol group can alter the activity of TRPV1. Consequently, we propose that such a modulation of the redox state might regulate the physiological activity of TRPV1.
KW - Capsaicin
KW - Dorsal root ganglion
KW - Sulfhydryl oxidation
KW - TRPV1
KW - Thimerosal
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U2 - 10.1016/j.neulet.2004.07.059
DO - 10.1016/j.neulet.2004.07.059
M3 - Article
C2 - 15464274
AN - SCOPUS:4644311541
SN - 0304-3940
VL - 369
SP - 250
EP - 255
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 3
ER -