Abstract
Two-pore domain K+ (K2P) channel activity is controlled by various stimuli that have been thought to finally converge at the selectivity filter (SF) gate. However, recent crystallographic studies have identified lower gates in TASK-1 and TASK-2 K2P channels but pharmacological means to open these gates are currently unknown. Here, we report that TALK-2 K2P channels also possess a lower gate by utilizing scanning mutagenesis, pore blocker analysis, permeant ion effects, chemical modification and MD simulations.
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