Bs. Karon et al., ANESTHETICS ALTER THE PHYSICAL AND FUNCTIONAL-PROPERTIES OF THE CA-ATPASE IN CARDIAC SARCOPLASMIC-RETICULUM, Biophysical journal, 68(3), 1995, pp. 936-945
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 chan
ges were detected by time-resolved phosphorescence anisotropy (TPA). L
idocaine inhibited and aggregated the Ca-ATPase in cardiac SR. Micromo
lar calcium or 0.5 M lithium chloride protected against lidocaine-indu
ced inhibition, indicating that electrostatic interactions are essenti
al to lidocaine inhibition of the Ca-ATPase. The phospholamban (PLB) a
ntibody 2D12, which mimics PLB phosphorylation, had no effect on lidoc
aine inhibition of the Ca-ATPase in cardiac SR. Inhibition and aggrega
tion of the Ca-ATPase in cardiac SR occurred at lower concentrations o
f lidocaine than necessary to inhibit and aggregate the Ca-ATPase in s
keletal SR, suggesting that the cardiac isoform of the enzyme has a hi
gher affinity for lidocaine. Halothane inhibited and aggregated the Ca
-ATPase in cardiac SR. Both inhibition and aggregation of the Ca-ATPas
e by halothane were much greater in the presence of PLB antibody or wh
en PLB was phosphorylated, indicating a protective effect of PLB on ha
lothane-induced inhibition and aggregation. The effects of halothane o
n cardiac SR are opposite from the effects of halothane observed in sk
eletal SR, where halothane activates and dissociates the Ca-ATPase. Th
ese results underscore the crucial role of protein-protein interaction
s on Ca-ATPase regulation and anesthetic perturbation of cardiac SR.