Abstract
Hydrogen peroxide, one of the reactive oxygen species (ROS), induces pain when it is applied to skin. However, receptor of hydrogen peroxide is unknown. Transient Receptor Potential A1 (TRPA1) channel is activated by pungent compounds such as allylisothiocianate (AITC), cinnamaldehyde, allicin and low temperatures. Kwan et al and Bautista et al report that pain is depressed in TRPA1 knockout mice, indicating that TRPA1 is a receptor that induces pain. These results lead us to hypothesize that TRPA1 is a receptor of hydrogen peroxide. Using Ca++ imaging and patch clamping, we aimed to verify this hypothesis. Hydrogen peroxide raised Ca++ concentration in TRPA1-expressing HEK293 cells. TRPA1 inhibitors (ruthenium red and camphor) suppressed this response. Under voltage-clamp mode (-60mV), hydrogen peroxide induced inward current in TRPA1-expressing HEK293 cells. In inside-out patch membrane excised from TRPA1-expressing HEK293 cells, single-channel activity appeared in response to hydrogen peroxide. To investigate whether TRPA1 is activated by hydrogen peroxide in sensory neurons, we recorded Ca++ imaging in cultured DRG neurons of mice. Most AITC-sensitive neurons were activated by hydrogen peroxide. We conclude that TRPA1 is a receptor of hydrogen peroxide. [J Physiol Sci. 2008;58 Suppl:S51]
