The molecular features of membrane perturbation by anaesthetic steroids: a study using differential scanning...

We have studied the interactions of the anaesthetic steroid alphaxalone and its inactive isomer delta 16-alphaxalone with model membrane bilayers using differential scanning calorimetry, small angle X-ray diffraction and solid state NMR. Our data show that the anaesthetic steroid broadens the membrane phase transition and increases the ratio of gauche to trans conformers in the membrane. Delta 16-Alphaxalone has only small effects on membrane and incorporates to a limited degree in the bilayer. The amphipathic anaesthetic steroid alphaxalone is located near the membrane interface (the junction of the polar and hydrophobic regions of the phospholipids forming the bilayer). It orients with its long axis parallel to the chains of the lipid membranes and its 3 alpha-hydroxyl group near the sn-2 carbonyl. Anchoring of the steroid at the membrane interface and imperfect packing with the bilayer chains may be involved in membrane perturbation and eventually lead to anaesthesia.