This study aims to elucidate the molecular target(s) of anesthetic action by creating knockout mice and examining the progeny for sensitivity to inhaled anesthetics. Six genetically altered mouse lines carrying mutations at GABAA receptor loci are proposed, specifically null alleles of a6, b3, g2, d subtypes, as well as point mutations of a6 and g2 subunits. These specific alleles have been chosen since inbred mice missing these alleles or carrying specific mutations have been shown previously to have altered sensitivity to anesthetic agents. After creation of the mouse strains, each will be tested for anesthetic sensitivity (5 volatile GAs on tail clamp/withdrawal MAC, loss of righting reflex), chloride flux experiments from brains of bred mice, and finally electrophysiologic studies to determine if single mutations change other neurons as well as characteristics of the channel with and without anesthetics. Hence behavioral and electrophysiology data are the endpoints of this project.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM052035-04
Application #
2519029
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1995-01-01
Project End
1998-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213