Back to Search
Start Over
Anesthetics alter the physical and functional properties of the Ca-ATPase in cardiac sarcoplasmic reticulum.
- Source :
-
Biophysical journal [Biophys J] 1995 Mar; Vol. 68 (3), pp. 936-45. - Publication Year :
- 1995
-
Abstract
- We have studied the effects of the local anesthetic lidocaine, and the general anesthetic halothane, on the function and oligomeric state of the CA-ATPase in cardiac sarcoplasmic reticulum (SR). Oligomeric changes were detected by time-resolved phosphorescence anisotropy (TPA). Lidocaine inhibited and aggregated the Ca-ATPase in cardiac SR. Micromolar calcium or 0.5 M lithium chloride protected against lidocaine-induced inhibition, indicating that electrostatic interactions are essential to lidocaine inhibition of the Ca-ATPase. The phospholamban (PLB) antibody 2D12, which mimics PLB phosphorylation, had no effect on lidocaine inhibition of the Ca-ATPase in cardiac SR. Inhibition and aggregation of the Ca-ATPase in cardiac SR occurred at lower concentrations of lidocaine than necessary to inhibit and aggregate the Ca-ATPase in skeletal SR, suggesting that the cardiac isoform of the enzyme has a higher affinity for lidocaine. Halothane inhibited and aggregated the Ca-ATPase in cardiac SR. Both inhibition and aggregation of the Ca-ATPase by halothane were much greater in the presence of PLB antibody or when PLB was phosphorylated, indicating a protective effect of PLB on halothane-induced inhibition and aggregation. The effects of halothane on cardiac SR are opposite from the effects of halothane observed in skeletal SR, where halothane activates and dissociates the Ca-ATPase. These results underscore the crucial role of protein-protein interactions on Ca-ATPase regulation and anesthetic perturbation of cardiac SR.
- Subjects :
- Animals
Anisotropy
Biophysical Phenomena
Biophysics
Calcium-Binding Proteins metabolism
Calcium-Transporting ATPases antagonists & inhibitors
Calcium-Transporting ATPases chemistry
Dogs
Enzyme Activation drug effects
Halothane pharmacology
In Vitro Techniques
Lidocaine pharmacology
Muscle, Skeletal drug effects
Muscle, Skeletal enzymology
Protein Conformation drug effects
Sarcoplasmic Reticulum drug effects
Sarcoplasmic Reticulum enzymology
Thermodynamics
Anesthetics pharmacology
Calcium-Transporting ATPases metabolism
Heart drug effects
Myocardium enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3495
- Volume :
- 68
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biophysical journal
- Publication Type :
- Academic Journal
- Accession number :
- 7756557
- Full Text :
- https://doi.org/10.1016/S0006-3495(95)80269-9