thomerosal에 의한 TRPV1 활성 조절

초록

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 (Icap) in cultured sensory neurons, in a reversible and dose-dependent manner, which was prevented by the co-application of the reducing agent, dithiothreitol. Other sulfhydryl oxidizing agents such as 5, 5’-dithio-bis-(2-nitrobenzoic acid) (DTNB), reduced glutathione (GSSG), Cu2+-phenathroline complex and hydrogen peroxide (H2O2) also blocked Icap reversibly. The inhibiting effect of thimerosal was also observed in HEK293 cells expressing VR1. Among the three cysteine residues of TRPV1 that are exposed to the extracellular space, the oxidation-induced effect of thimerosal on Icap 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.