2 research outputs found
Xenon and Other Volatile Anesthetics Change Domain Structure in Model Lipid Raft Membranes
Inhalation anesthetics have been
in clinical use for over 160 years,
but the molecular mechanisms of action continue to be investigated.
Direct interactions with ion channels received much attention after
it was found that anesthetics do not change the structure of homogeneous
model membranes. However, it was recently found that halothane, a
prototypical anesthetic, changes domain structure of a binary lipid
membrane. The noble gas xenon is an excellent anesthetic and provides
a pivotal test of the generality of this finding, extended to ternary
lipid raft mixtures. We report that xenon and conventional anesthetics
change the domain equilibrium in two canonical ternary lipid raft
mixtures. These findings demonstrate a membrane-mediated mechanism
whereby inhalation anesthetics can affect the lipid environment of
transmembrane proteins
Direct Evidence of Conformational Changes Associated with Voltage Gating in a Voltage Sensor Protein by Time-Resolved X‑ray/Neutron Interferometry
The
voltage sensor domain (VSD) of voltage-gated cation (e.g.,
Na<sup>+</sup>, K<sup>+</sup>) channels central to neurological signal
transmission can function as a distinct module. When linked to an
otherwise voltage-insensitive, ion-selective membrane pore, the VSD
imparts voltage sensitivity to the channel. Proteins homologous with
the VSD have recently been found to function themselves as voltage-gated
proton channels or to impart voltage sensitivity to enzymes. Determining
the conformational changes associated with voltage gating in the VSD
itself in the absence of a pore domain thereby gains importance. We
report the direct measurement of changes in the scattering-length
density (SLD) profile of the VSD protein, vectorially oriented within
a reconstituted phospholipid bilayer membrane, as a function of the
transmembrane electric potential by time-resolved X-ray and neutron
interferometry. The changes in the experimental SLD profiles for both
polarizing and depolarizing potentials with respect to zero potential
were found to extend over the entire length of the isolated VSD’s
profile structure. The characteristics of the changes observed were
in qualitative agreement with molecular dynamics simulations of a
related membrane system, suggesting an initial interpretation of these
changes in terms of the VSD’s atomic-level 3-D structure