Polymodal activation of the TREK-2 K2P channel produces structurally distinct open states

• DOI: 10.1085/jgp.201611601
• Publication Date: 2016-05-30T13:14:31Z
• Authors: Conor McClenaghan; Marcus Schewe; Prafulla Aryal; Elisabeth P. Carp...; Thomas Baukrowitz; Stephen J. Tucker
• Keywords: Subfamily

The TREK subfamily of two-pore domain (K2P) K+ channels exhibit polymodal gating by a wide range physical and chemical stimuli. Crystal structures now exist for these in two main states referred to as the “up” “down” conformations. However, recent studies have resulted contradictory mutually exclusive conclusions about functional (i.e., conductive) status To address this problem, we used state-dependent TREK-2 inhibitor norfluoxetine that can only bind down state, thereby allowing us distinguish between conformations when activated different Our results reconcile previously models demonstrating activation pressure, temperature, voltage, pH produce more than one structurally distinct open state reveal channel does not simply involve switching up These also highlight diversity structural mechanisms K2P use integrate signals.