Premium
Sites and functional consequence of VDAC–alkylphenol anesthetic interactions
Author(s) -
Weiser Brian P.,
Bu Weiming,
Wong David,
Eckenhoff Roderic G.
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.10.009
Subject(s) - voltage dependent anion channel , gating , biophysics , vdac1 , chemistry , anesthetic , lipid bilayer , propofol , gramicidin , biochemistry , bacterial outer membrane , microbiology and biotechnology , biology , membrane , pharmacology , medicine , anesthesia , escherichia coli , gene
General anesthetics have previously been shown to bind mitochondrial VDAC. Here, using a photoactive analog of the anesthetic propofol, we determined that alkylphenol anesthetics bind to Gly56 and Val184 on rat VDAC1. By reconstituting rat VDAC into planar bilayers, we determined that propofol potentiates VDAC gating with asymmetry at the voltage polarities; in contrast, propofol does not affect the conductance of open VDAC. Additional experiments showed that propofol also does not affect gramicidin A properties that are sensitive to lipid bilayer mechanics. Together, this suggests propofol affects VDAC function through direct protein binding, likely at the lipid‐exposed channel surface, and that gating can be modulated by ligand binding to the distal ends of VDAC β‐strands where Gly56 and Val184 are located.