The KvLm Potassium Channel in Asymmetric Bilayer

Abstract

Bilayer lipid composition and charge asymmetry markedly alter the inactivation phenotype of a voltage-gated K+ channel1. Here we investigate the effects of lipid head-group size and charge asymmetry on the permeation and gating of a sensor-less pore module from a voltage-gated potassium-selective ion channel (KvLm-PM) by using Droplet Interface Bilayers (DIBs). In DIBs a lipid bilayer is formed by contacting two aqueous droplets submerged in the hydrocarbon medium2. When each droplet contains a different lipid an asymmetric bilayer forms at the droplet interface. Five lipids of equal carbon chain length that differ in their head-group size and charge were selected to supplement DPhPC bilayers and form both symmetric and asymmetric bilayers. We found that a negative charge in either leaflet favors channel opening. Head-group charge also affects the unitary conductance of KvLm-PM. For example when both leaflets are negative, the conductance is increased.1Schmidt D, MacKinnon R. Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane. Proc. Nat. Acad. Sci. USA 2008 DEC 9; 105(49): 19276-19281.2Hagan Bayley et al. Droplet interface bilayers. Mol. BioSyst., 2008, 4, 1191-1208.