A photoswitchable inhibitor of TREK channels controls pain in wild-type intact freely moving animals.

ABSTRACT: By endowing light control of neuronal activity, optogenetics and photopharmacology are powerful methods notably used to probe the transmission of pain signals. However, costs, animal handling and ethical issues have reduced their dissemination and routine use. Here we report LAKI (Light Activated K⁺ channel Inhibitor), a specific photoswitchable inhibitor of the pain-related two-pore-domain potassium TREK and TRESK channels. In the dark or ambient light, LAKI is inactive. However, alternating transdermal illumination at 365 nm and 480 nm reversibly blocks and unblocks TREK/TRESK current in nociceptors, enabling rapid control of pain and nociception in intact and freely moving mice and nematode. These results demonstrate, in vivo, the subcellular localization of TREK/TRESK at the

SUBMITTER: Landra-Willm A 

PROVIDER: S-EPMC9977718 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature