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Journal Articles PLoS Computational Biology Year : 2012

General Anesthetics Predicted to Block the GLIC Pore with Micromolar Affinity

David N. Lebard
  • Function : Author
Roderic G. Eckenhoff
  • Function : Author
Michael L. Klein
  • Function : Author
Grace Brannigan
  • Function : Author

Abstract

Author Summary

Although general anesthesia is performed every day on thousands of people, its detailed microscopic mechanisms are not known. What is known is that general anesthetic drugs modulate the activity of ion channels in the central nervous system. These channels are proteins that open in response to binding of neurotransmitter molecules, creating an electric current through the cell membrane and thus propagating nerve impulses between cells. One possible mechanism for ion channel inhibition by anesthetics is that the drugs bind inside the pore of the channels, blocking ion current. Here we investigate such a pore block mechanism by computing the strength of the drugs\textquoteright interaction with the pore \textendash and hence the likelihood of binding, in the case of GLIC, a bacterial channel protein. The results, obtained from numerical simulations of atomic models of GLIC, indicate that the anesthetics isoflurane and propofol have a tendency to bind in the pore that is strong enough to explain blocking of the channel, even at low concentration of the drugs.

Domains

Biophysics

Dates and versions

hal-01498104 , version 1 (29-03-2017)

Identifiers

Cite

David N. Lebard, Jérôme Hénin, Roderic G. Eckenhoff, Michael L. Klein, Grace Brannigan. General Anesthetics Predicted to Block the GLIC Pore with Micromolar Affinity. PLoS Computational Biology, 2012, 8 (5), pp.e1002532. ⟨10.1371/journal.pcbi.1002532⟩. ⟨hal-01498104⟩
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