Integrated Calendar

I will discuss a particular case of the AdS3/CFT2 higher spin duality which connects to a putative tensionless limit of AdS3 string theories. I will describe how the higher spin symmetries provide a natural way to organise the extended stringy symmetries of such a limit.

Some of the fascinating features of voltage-sensing domains (VSD) in voltage-gated cation channels (VGCC) are their modular nature and adaptability. Here we examined the VSD promiscuity of VGCC, using non-toxin gating-modifiers, NH17 and NH29, which share closely related structures and stabilize Kv7.2 potassium channels, in the closed and open state, respectively. NH17 and NH29 exert opposite gating-modifier effects on TRPV1 channels,
operating respectively, as an activator and a blocker of TRPV1 currents. Combined mutagenesis and electrophysiology, structural homology modeling, molecular docking and molecular dynamics simulation indicate that both compounds target the VSD of TRPV1 channels, which like vanilloids are involved in π-π stacking, H-bonding and hydrophobic interactions. Reflecting the VSD promiscuity, they also affect the lone VSD proton channel mVSOP. Remarkably, NH29 alleviates neuropathic pain in rats, suggesting that sometimes, promiscuous VSD ligands may be therapeutically beneficial. Thus, structurally related, yet different molecules can interact with the VSD of the same VGCC, while the same gating-modifier can promiscuously interact with different VGCC. Subtle differences at the VSD-ligand interface will dictate whether the gating-modifier stabilizes channels in either the closed or the open state.