The effects of stretch activation on ionic selectivity of the TREK-2 K2P K+ channel

摘要

The TREK-2 (KCNK10 ) K2P potassium channel can be regulated by variety of polymodal stimuli including pressure. In a recent study, we demonstrated that this mechanosensitive K~(+) channel responds to changes in membrane tension by undergoing a major structural change from its ‘down’ state to the more expanded ‘up’ state conformation. These changes are mostly restricted to the lower part of the protein within the bilayer, but are allosterically coupled to the primary gating mechanism located within the selectivity filter. However, any such structural changes within the filter also have the potential to alter ionic selectivity and there are reports that some K2Ps, including TREK channels, exhibit a dynamic ionic selectivity. In this addendum to our previous study we have therefore examined whether the selectivity of TREK-2 is altered by stretch activation. Our results reveal that the filter remains stable and highly selective for K~(+) over Na~(+) during stretch activation, and that permeability to a range of other cations (Rb~(+), Cs~(+) and NH_(4)~(+)) also does not change. The asymmetric structural changes that occur during stretch activation therefore allow the channel to respond to changes in membrane tension without a loss of K~(+) selectivity.