Altered Anesthetic Sensitivity of Mice Lacking Ndufs4, a Subunit of Mitochondrial Complex I
Quintana Romero, Albert (University of Washington. Howard Hughes Medical Institute and Department of Biochemistry)
Morgan, Philip G. (University of Washington. Department of Anesthesiology and Pain Medicine)
Kruse, Shane E. (University of Washington. Howard Hughes Medical Institute and Department of Biochemistry)
Sedensky, Margaret M. (Seattle Children's Research Institute)

Data:	2012
Resum:	Anesthetics are in routine use, yet the mechanisms underlying their function are incompletely understood. Studies in vitro demonstrate that both GABAA and NMDA receptors are modulated by anesthetics, but whole animal models have not supported the role of these receptors as sole effectors of general anesthesia. Findings in C. elegans and in children reveal that defects in mitochondrial complex I can cause hypersensitivity to volatile anesthetics. Here, we tested a knockout (KO) mouse with reduced complex I function due to inactivation of the Ndufs4 gene, which encodes one of the subunits of complex I. We tested these KO mice with two volatile and two non-volatile anesthetics. KO and wild-type (WT) mice were anesthetized with isoflurane, halothane, propofol or ketamine at post-natal (PN) days 23 to 27, and tested for loss of response to tail clamp (isoflurane and halothane) or loss of righting reflex (propofol and ketamine). KO mice were 2. 5 - to 3- fold more sensitive to isoflurane and halothane than WT mice. KO mice were 2-fold more sensitive to propofol but resistant to ketamine. These changes in anesthetic sensitivity are the largest recorded in a mammal.
Nota:	RDP and AQ were supported by the Howard Hughes Medical Institute (HHMI). AQ was a recipient of MICINN postdoctoral mobility program fellowship from the Spanish Ministerio de Ciencia e Innovación. PGM and MMS were supported by National Institutes of Health (NIH) grant GM58881. These studies were also supported in part by the Mitochondrial Research Guild. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Anestèsics ; Efectes fisiològics ; Proves ; Anestesiologia
Publicat a:	PloS one, Vol. 7, Num. 8 (2012) , p. e42904, ISSN 1932-6203

DOI: 10.1371/journal.pone.0042904
PMID: 22912761

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