Inhibition of plasma membrane Ca(2+)-ATPase activity by volatile anesthetics.

Article Details

Citation

Copy to clipboard

Kosk-Kosicka D, Roszczynska G

Inhibition of plasma membrane Ca(2+)-ATPase activity by volatile anesthetics.

Anesthesiology. 1993 Oct;79(4):774-80.

PubMed ID

8214757 [ View in PubMed

]

Abstract

BACKGROUND: The precise sites and mechanisms of action of volatile anesthetics remain unknown. Recently, several integral membrane proteins have been suggested as potential targets to which anesthetics can bind at hydrophobic regions. Impairment of cell Ca2+ homeostasis has been postulated as one of the possible mechanisms of anesthetic action. To test these hypotheses, the authors selected the human erythrocyte Ca(2+)-ATPase as a model membrane protein. This enzyme is an integral membrane protein that is instrumental in maintaining Ca2+ homeostasis in the cell in which it is the sole Ca(2+)-transporting system. Thus, any functional alteration of the Ca(2+)-ATPase by anesthetics may lead to serious perturbations in Ca(2+)-regulated processes in the cell. METHODS: The Ca(2+)-ATPase activity was measured as a function of increased concentration of four volatile anesthetics: halothane, isoflurane, enflurane, and desflurane. RESULTS: All four anesthetics significantly inhibited the Ca(2+)-ATPase activity in a dose-dependent manner. The half-maximal inhibition occurred at anesthetic concentrations from 0.3 to 0.7 vol% at 37 degrees C, which, except for desflurane, is a clinically relevant concentration range. The greater the clinical potency of the volatile anesthetics studied, the less was the concentration required to inhibit the Ca(2+)-ATPase activity. The inhibition was less at 25 degrees C than at 37 degrees C, which is consistent with direct interactions of the nonpolar interfaces of the enzyme with the nonpolar of the portions of the anesthetics. CONCLUSIONS: The authors' findings indicate that the Ca(2+)-ATPase is a suitable model for investigating the mechanism of action of volatile anesthetics on the integral membrane protein, and that this inhibition may be specific.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Desflurane	ATP synthase subunit delta, mitochondrial	Protein	Humans	Unknown	Other/unknown	Details
Enflurane	Calcium-transporting ATPase type 2C member 1	Protein	Humans	Unknown	Inhibitor	Details
Enflurane	Sarcoplasmic/endoplasmic reticulum calcium ATPase 1	Protein	Humans	Unknown	Inhibitor Stimulator	Details
Isoflurane	Calcium-transporting ATPase type 2C member 1	Protein	Humans	Yes	Inhibitor	Details