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Accueil > Animation Scientifique > Année 2013

Conférence Dr. Vincenzo Carnevale

Le mercredi 9 octobre 2013 à 11h en Salle Jean Barriol,
Faculté des Sciences et Technologies, Entrée 2A, Niveau 7,
 
le Dr. Vincenzo Carnevale, Temple University (Philadelphia, E.U.),
http://scholar.google.fr/citations?sortby=pubdate&hl=en&user=q6vxyRIAAAAJ&view_op=list_works
 
donnera une conférence intitulée :
 
"Volatile General Anesthetic Interactions with Voltage-Gated
Sodium Channels"
 
-contact : M. Tarek - Mounir.Tarek@univ-lorraine.fr-

Abstract
The molecular mechanisms mediating the pharmacologically induced state of general anesthesia are, in general, poorly understood. Modulation of voltage gated sodium channels is thought to play a major role in anesthesia, as several members of this class of channels show a significant response to general anesthetics. Molecular dynamics simulations performed on one of these voltage gated channels, NaChBac, revealed binding sites and access pathways for the volatile general anesthetic isoflurane. Unbiased “flooding” simulations and cluster analysis allowed us to identify all the possible binding sites ; free energy perturbation theory was then used to calculate binding affinities. At physiologically relevant concentrations, isoflurane binds the channel at three distinct sites. One site is in the pore of the channel and is possibly responsible for pore block. Surprisingly, this binding site is accessible to the drug even when the channel is closed. The “fenestrations” present in the membrane-embedded region of the channel seemingly act as the long-hypothesized hydrophobic drug access pathway.
 


 

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