Patient with anaesthesiaAnaesthesia makes up the largest hospital speciality and has a huge role to play in nearly every aspect of any hospital from operating theatres to accident and emergency, to the labour ward, and to intensive care. Our research ranges from basic molecular research into mechanisms of anaesthesia to investigating the clinical impact of novel anaesthetic agents. 

Our research covers the entirety of patient’s perioperative journey and through this, we aim to deliver the greatest impact. The section has been pioneering in the development of novel technologies to facilitate the delivery of anaesthetic agents and has also made pivotal in-roads into the mechanism of action of anaesthetic agents and their wider application to other diseases (such as their protective roles in brain injury and in cancer).

Research themes:

Citation

BibTex format

@article{Armstrong:2012:10.1097/ALN.0b013e31825ada2e,
author = {Armstrong, SP and Banks, PJ and McKitrick, TJW and Geldart, CHG and Edge, CJE and Babla, R and Simillis, C and Franks, NP and Dickinson, R},
doi = {10.1097/ALN.0b013e31825ada2e},
journal = {Anesthesiology},
pages = {38--47},
title = {Identification of two mutations (F758W & F758Y) in the NMDA receptor glycine-binding site that prevent competitive inhibition by xenon without affecting glycine binding},
url = {http://dx.doi.org/10.1097/ALN.0b013e31825ada2e},
volume = {117},
year = {2012}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Xenon is a general anesthetic with neuroprotective properties. Xenon inhibition at the glycine-binding site of the N-Methyl-D-aspartate (NMDA) receptor mediates xenon neuroprotection against ischemic injury in vitro. Here we identify specific amino acids important for xenon binding to the NMDA receptor, with the aim of finding silent mutations that eliminate xenon binding but leave normal receptor function intact.METHODS:Site-directed mutagenesis was used to mutate specific amino-acids in the GluN1 subunit of rat NMDA receptors. Mutant GluN1/GluN2A receptors were expressed in HEK 293 cells and were assessed functionally using patch-clamp electrophysiology. The responses of the mutant receptors to glycine and anesthetics were determined.RESULTS:Mutation of phenylalanine 758 to an aromatic tryptophan or tyrosine left glycine affinity unchanged, but eliminated xenon binding without affecting the binding of sevoflurane or isoflurane.CONCLUSIONS:These findings confirm xenon binds to the glycine site of the GluN1 subunit of the NMDA receptor and indicate that interactions between xenon and the aromatic ring of the phenylalanine 758 residue are important for xenon binding. Our most important finding is that we have identified two mutations, F758W and F758Y, that eliminate xenon binding to the NMDA receptor glycine site without changing the glycine affinity of the receptor or the binding of volatile anesthetics. The identification of these selective mutations will allow knock-in animals to be used to dissect the mechanism(s) of xenon's neuroprotective and anesthetic properties in vivo.
AU  - Armstrong,SP
AU  - Banks,PJ
AU  - McKitrick,TJW
AU  - Geldart,CHG
AU  - Edge,CJE
AU  - Babla,R
AU  - Simillis,C
AU  - Franks,NP
AU  - Dickinson,R
DO  - 10.1097/ALN.0b013e31825ada2e
EP  - 47
PY  - 2012///
SN  - 1528-1175
SP  - 38
TI  - Identification of two mutations (F758W & F758Y) in the NMDA receptor glycine-binding site that prevent competitive inhibition by xenon without affecting glycine binding
T2  - Anesthesiology
UR  - http://dx.doi.org/10.1097/ALN.0b013e31825ada2e
UR  - http://hdl.handle.net/10044/1/26436
VL  - 117
ER  -
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