The molecular mechanism(s) through which volatile anesthetics produce their effects remain unknown. Recent data suggests that the effects of anesthetics are mediated by selective alterations in membrane ion fluxes. The goals of this proposal are to characterize the structural interactions of volatile anesthetic molecules with specific membrane proteins involved in ion translocation, and to determine how these interactions result in modulation of protein function. To achieve these goals, two proteins known to be inhibited by volatile anesthetics will be studied. Structural studies will focus on the erythrocyte anion exchange (Band 3) protein, an abundant protein with known primary structure and readily measured function. Radiochemical and NMR spectroscopic techniques will be used to: (1) Measure and characterize the association of volatile anesthetics with purified Band 3 protein; and (2) Identify the specific sites on Band 3 protein with which anesthetic 'molecules interact. Volatile anesthetic inhibition of anion exchange will also be studied, so that functional effects of volatile anesthetics on Band 3 can be correlated with the results of structural studies. A second protein, the L-type voltage-dependent calcium channel, will be used to examine the mechanism of volatile anesthetic inhibition of ion channel function. The effects of volatile anesthetics on L-channels will be explored using specific biochemical probes of Ca2+ channel conformation in conjunction with manipulation and measurement of channel function. Collectively, the results of the proposed studies should provide significant insight into the-mechanisms through which volatile anesthetics perturb protein function and ultimately produce their physiological effects.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM037846-06
Application #
3293672
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1986-12-01
Project End
1995-11-30
Budget Start
1991-12-15
Budget End
1992-11-30
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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