Volatile Anesthetics Selectively Inhibit the Ca²⁺-transporting ATPase in Neuronal and Erythrocyte Plasma Membranes

Background: The activity of the plasma membrane Ca²⁺-transporting adenosine triphosphatase (PMCA) is inhibited by volatile anesthetics at clinical concentrations. The goal of the current study was to determine whether the inhibition is selective as compared to other adenosine triphosphatases (ATPases) and another group of general anesthetics, barbiturates. In addition, the authors determined whether the response to anesthetics of the enzymes in neuronal membranes is similar to that in erythrocyte membranes. Methods: The effects of halothane, isoflurane, and sodium pentobarbital on four different ATPase activities were studied at 37°C in two distinct plasma membrane preparations, human red blood cells and synaptosomal membranes from rat cerebellum. Results: Inhibition patterns of the PMCA by halothane and isoflurane at anesthetic concentrations were very similar in red blood cells and synaptosomal membranes. The half-maximal inhibition (I₅₀) occurred at 0.25-0.30 mM halothane and 0.30-0.32 mM isoflurane. The PMCA in both membranes was significantly more sensitive to the inhibitory action of volatile anesthetics (I₅₀ = 0.75-1.15 minimum alveolar concentration) than were other ATPases, such as the Na⁺,K⁺-ATPase (I₅₀ ≈ 3 minimum alveolar concentration) or Mg²⁺-ATPaSe (I₅₀ ≥ 5 minimum alveolar concentration). In contrast, sodium pentobarbital inhibited the PMCA in both membranes only at ≈100-200-fold above its anesthetic concentrations. The other ATPases were inhibited at similar pentobarbital concentrations (I₅₀ = 11-22 mM). Conclusions: The findings demonstrate analogous response of the PMCA of neuronal and erythrocyte cells to two groups of general anesthetics. The PMCA activity is selectively inhibited by volatile anesthetics at their clinical concentrations. The enzyme in vivo may then be a pharmacologic target for volatile anesthetics but not for barbiturates.