The Molecular Features of Membrane Perturbation by Anaesthetic Steroids: A Study Using Differential Scanning Calorimetry, Small Angle X-Ray Diffraction and Solid State 2H NMR

  1. Derek Chadwick Organizer and
  2. Kate Widdows
  1. Alexandros Makriyannis1,2,3,
  2. De-Ping Yang1,3 and
  3. Thomas Mavromoustakos1,3

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513989.ch10

Ciba Foundation Symposium 153 - Steroids and Neuronal Activity

Ciba Foundation Symposium 153 - Steroids and Neuronal Activity

How to Cite

Makriyannis, A., Yang, D.-P. and Mavromoustakos, T. (2007) The Molecular Features of Membrane Perturbation by Anaesthetic Steroids: A Study Using Differential Scanning Calorimetry, Small Angle X-Ray Diffraction and Solid State 2H NMR, in Ciba Foundation Symposium 153 - Steroids and Neuronal Activity (eds D. Chadwick and K. Widdows), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513989.ch10

Author Information

  1. 1

    Section of Medicinal Chemistry & Pharmacognosy, School of Pharmacy, and Institute of Materials Science, University of Connecticut, Storrs, CT 06269, USA

  2. 2

    Medicinal Chemistry U-92, University of Connecticut, Storrs, CT 06268, USA

  3. 3

    Francis Bitter National Magnet Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471926894

Online ISBN: 9780470513989

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Keywords:

  • membrane perturbation;
  • X-ray diffraction;
  • differential scanning calorimetry;
  • anaesthetic steroids;
  • electron spin resonance

Summary

We have studied the interactions of the anaesthetic steroid alphaxalone and its inactive isomer Δ16-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. Δ16-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 3α-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.