Page 44 - Q. Neuroscience

[Q. Neuroscience-26]

The role of Anoctamin 8/TMEM16H in the nociception

Huan-jun Lu¹, Thien-Luan Nguyen¹, Hyungsup Kim¹, Hyesu Kim¹, Sungmin Pak¹, Jaehyouk Choi¹,
Taewoong Ha¹, Sujin Lim¹, Kyungmin Kim¹, Mi-Sun Kim¹, Gyu-Sang Hong¹, Uhtaek Oh¹˙*

¹Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, ROK

The Anoctamin (ANO, or TMEM16) gene family consists of ten isoforms. ANO1 and ANO2 are identified as Ca2+-

activated anion channels. ANO6 is a lipid scramblase disrupting polarized phospholipids in the membrane. However,
the function of ANO8 is not known. Here we found that ANO8/TMEM16H is a cAMP-activated cation channel.

Intracellular cAMP-induced robust currents when heterologously expressed in mammalian cells. The cAMP-
dependent currents were inhibited by a protein kinase-A inhibitor, suggesting the active role of protein kinase A in

its activation mechanism. A cholera toxin, an activator of adenylate cyclase also activated ANO8. The cAMP-induced
currents in ANO8-expressing cells were cationic, which did not discriminate among cations. ANO8 is highly

expressed in neurons in the brain regions as well as dorsal root ganglion neurons. The knockdown of Ano8 causes
a decrease in cAMP-dependent currents in dorsal root ganglion neurons as well as nociceptive behaviors. These

results now suggest that ANO8 is a cation channel activated by the cAMP/pathway and involved in nociception in
the pain pathway.