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Related Experiment Videos

Depression of phase-transition temperature by anesthetics: nonzero solid membrane binding.

Y Kaminoh1, C Tashiro, H Kamaya

  • 1Department of Anesthesia, University of Utah School of Medicine, Salt Lake City.

Biochimica Et Biophysica Acta
|December 22, 1988
PubMed
Summary

Anesthetics bind to both liquid-crystal and solid-gel phospholipid membranes, influencing membrane transition temperatures. This study presents a theory to quantify anesthetic binding and its effect on membrane phase transitions, revealing partition coefficients are key to transition broadening.

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Area of Science:

  • Biochemistry
  • Physical Chemistry
  • Membrane Biophysics

Background:

  • Anesthetic effects on phospholipid membrane phase transition temperatures are typically analyzed using the van't Hoff model, which assumes no anesthetic interaction with solid-gel membranes.
  • However, anesthetics demonstrably bind to solid-gel membranes, necessitating a more nuanced understanding of their interaction with different membrane states.
  • Investigating the differential binding of anesthetics to liquid-crystal versus solid-gel membranes is crucial for elucidating anesthetic mechanisms of action at the lipid membrane level.

Purpose of the Study:

  • To develop a theoretical framework for estimating anesthetic binding to both liquid-crystal and solid-gel states of phospholipid membranes at their phase-transition temperature.
  • To establish the relationship between anesthetic partition coefficients and their impact on membrane transition characteristics, including transition temperature shifts and transition broadening.

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  • To analyze previously published data on local anesthetics and dipalmitoylphosphatidylcholine (DPPC) vesicle membranes using the developed theoretical model.

    • Main Methods:

    • Derivation of theoretical equations to quantify anesthetic binding to distinct membrane phases (liquid-crystal and solid-gel) at the phase-transition temperature.
    • Relating partition coefficients of anesthetics to their observed effects on the membrane's phase transition temperature and the width of this transition.
    • Application of the derived theory to re-analyze existing experimental data concerning local anesthetic interactions with DPPC vesicle membranes.

    Main Results:

    • The developed theory provides equations linking anesthetic partition coefficients to changes in transition temperature and transition broadening.
    • The study indicates that the breadth of the phase transition temperature is primarily governed by the membrane/buffer partition coefficients of the anesthetics.
    • Numerical values for local anesthetic partitioning into liquid-crystal and solid-gel DPPC membranes at the phase transition were calculated: procaine (8.0x10^3, 4.7x10^3), lidocaine (3.7x10^3, 2.3x10^3), bupivacaine (4.1x10^4, 2.6x10^4), and tetracaine (7.3x10^4, 4.7x10^4).

    Conclusions:

    • A theoretical model was established to accurately estimate anesthetic binding to different phospholipid membrane states.
    • Anesthetic partition coefficients are critical determinants of the broadening of the membrane phase transition.
    • The findings provide quantitative insights into the differential interaction of local anesthetics with lipid membranes, advancing the understanding of anesthetic action.