UVA Light Triggers Activation of TRPV1 and TRPA1 by Staurosporine and Midostaurin

The activation of TRPV1 and TRPA1 by UVA light is a complex process involving channel modulation by reactive oxygen species (ROS). The present study describes staurosporine and midostaurin, two protein kinase inhibitors, as photosensitizers that can modulate the activity of TRPV1 and TRPA1 in a UVA light-dependent manner. Patch-clamp and calcium imaging were used to investigate effects of staurosporine and midostaurin on recombinant human (h) TRPV1 and TRPA1 in HEK 293T cells and on native mouse dorsal root ganglion (DRG) cells. Staurosporine applied alone did not induce channel activation, but co-application with UVA light activated both TRPV1 and TRPA1. Staurosporine with UVA light also potentiated TRPV1-mediated membrane currents induced by heat and protons. Midostaurin induced the UVA light-independent activation and sensitization of TRPV1 and TRPA1, and this effect was strongly potentiated by UVA light. Effects induced by both staurosporine and midostaurin were reversed by the reducing agent dithiothreitol (DTT). Midostaurin induced a calcium influx in TRPA1-expressing DRG neurons. Our results show that staurosporine and midostaurin modulate the activity of TRPV1 and TRPA1 channels in the presence of UVA light. These photosensitizing properties can be relevant when staurosporine is used for in vitro experiments, and they may account for the phototoxic side effects of midostaurin.