TY - JOUR TI - Molecular mechanism of voltage-dependent potentiation of KCNH potassium channels AU - Dai, Gucan AU - Zagotta, William N A2 - Chanda, Baron VL - 6 PY - 2017 DA - 2017/04/26 SP - e26355 C1 - eLife 2017;6:e26355 DO - 10.7554/eLife.26355 UR - https://doi.org/10.7554/eLife.26355 AB - EAG-like (ELK) voltage-gated potassium channels are abundantly expressed in the brain. These channels exhibit a behavior called voltage-dependent potentiation (VDP), which appears to be a specialization to dampen the hyperexitability of neurons. VDP manifests as a potentiation of current amplitude, hyperpolarizing shift in voltage sensitivity, and slowing of deactivation in response to a depolarizing prepulse. Here we show that VDP of D. rerio ELK channels involves the structural interaction between the intracellular N-terminal eag domain and C-terminal CNBHD. Combining transition metal ion FRET, patch-clamp fluorometry, and incorporation of a fluorescent noncanonical amino acid, we show that there is a rearrangement in the eag domain-CNBHD interaction with the kinetics, voltage-dependence, and ATP-dependence of VDP. We propose that the activation of ELK channels involves a slow open-state dependent rearrangement of the direct interaction between the eag domain and CNBHD, which stabilizes the opening of the channel. KW - FRET KW - noncanonical amino acid KW - unnatural amino acid KW - patch-clamp fluorometry KW - ELK KW - Anap JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -