Showing papers by "Thomas Baukrowitz published in 2016"
TL;DR: V voltage-dependent gating is common to most K2P channels and that this voltage sensitivity originates from the movement of three to four ions into the high electric field of an inactive selectivity filter, providing insight into the functional plasticity of a K+-selective filter.
158 citations
TL;DR: McClenaghan et al. show that the channel can be open in both of these conformations and that gating is primarily achieved by the channel’s selectivity filter.
Abstract: The TREK subfamily of two-pore domain (K2P) K+ channels exhibit polymodal gating by a wide range of physical and chemical stimuli. Crystal structures now exist for these channels in two main states referred to as the “up” and “down” conformations. However, recent studies have resulted in contradictory and mutually exclusive conclusions about the functional (i.e., conductive) status of these two conformations. To address this problem, we have used the state-dependent TREK-2 inhibitor norfluoxetine that can only bind to the down state, thereby allowing us to distinguish between these two conformations when activated by different stimuli. Our results reconcile these previously contradictory gating models by demonstrating that activation by pressure, temperature, voltage, and pH produce more than one structurally distinct open state and reveal that channel activation does not simply involve switching between the up and down conformations. These results also highlight the diversity of structural mechanisms that K2P channels use to integrate polymodal gating signals.
57 citations
TL;DR: Voltage-dependent gating is common to most K2P channels and that this voltage sensitivity originates from the movement of 3-4 ions into the high electric field of an inactive selectivity filter, which provides insight into the functional plasticity of a K+-selective filter.
2 citations