Anesthetics alter the physical and functional properties of the Ca-ATPase in cardiac sarcoplasmic reticulum

Biophys J. 1995 Mar;68(3):936-45. doi: 10.1016/S0006-3495(95)80269-9.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anesthetics / pharmacology*
  • Animals
  • Anisotropy
  • Biophysical Phenomena
  • Biophysics
  • Calcium-Binding Proteins / metabolism
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Calcium-Transporting ATPases / chemistry
  • Calcium-Transporting ATPases / metabolism*
  • Dogs
  • Enzyme Activation / drug effects
  • Halothane / pharmacology
  • Heart / drug effects*
  • In Vitro Techniques
  • Lidocaine / pharmacology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / enzymology
  • Myocardium / enzymology*
  • Protein Conformation / drug effects
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / enzymology
  • Thermodynamics


  • Anesthetics
  • Calcium-Binding Proteins
  • phospholamban
  • Lidocaine
  • Calcium-Transporting ATPases
  • Halothane