Nicolas Lee L&S Biological Sciences
Cannabinoid inhibition of mechanosensitive K+ channels
Epilepsy will affect 1 in 26 people throughout their life, and is currently active in about 2.9 million U.S. adults. It remains difficult to treat, with many patients continuing to experience seizures despite being medicated. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, has become prominent in clinical settings for its anti-epileptic effects. Even so, the molecular basis behind CBD’s anti-epileptic effects remain unknown. Recent studies at the Brohawn Lab have illustrated CBD as a potent inhibitor of mechanosensitive two-pore domain K+ (K2P) channels, including TRAAK and TREK-1 that regulate electric signaling in neurons (Docter et. al, 2024). 5 TRAAK mutations have been reported to be related to epileptic and neurodevelopmental disorders in humans (Krygier et. al, 2024). They discovered that these mutants retain sensitivity to CBD, suggesting CBD may be viable for patients with these mutations. This proposed project aims to gain some insight into the molecular basis of CBD’s antiepileptic effects, by determining CBD’s mechanism of inhibition of TRAAK channels.
Message To Sponsor
Thank you to the Leadership Fund for sponsoring my project this summer! Throughout my exploration of the molecular mechanisms behind TRAAK channel inhibition by CBD, I was able to learn crucial laboratory skills including but not limited to: intracellular and extracellular electrophysiology, protein expression and purification, and polymerase chain reaction. This experience has further developed my interest in structural biology, and will be a deciding factor in what I choose to pursue in a PhD program.