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

B. S. Karon, L. M. Geddis, H. Kutchai, D. D. Thomas

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45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)936-945
Number of pages10
JournalBiophysical journal
Issue number3
StatePublished - 1995

Bibliographical note

Funding Information:
We thank Dr. Joseph J. Feher, Medical College of Virginia, for the generous gift ofCSR. We are also pleased to thank Dr. Larry Jones, Indiana University School of Medicine, for the anti-PLB Ab 2D12. We also thank James Mahaney, Razvan Cornea, and Joe Mersol for their help and Nicoleta Cornea, John Matta, and Bob Bennett for technical support. D. D. T. was supported by National Institutes of Health (NIH) Grant GM27906. H. K. was supported by Grant-in-Aid VA-93-G-20 from the American Heart Association, Virginia, and NIH Grant GMS0764. B. S. K. was supported in part by a NIH predoctoral training grant


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