Inhibition of Na-Ca exchange by general anesthetics.

Abstract

General anesthetics, typically octanol, were found to inhibit the influx of calcium in isolated sodium-loaded adult rat heart cells, using ^Ca, quin 2, or indo 1. Inhibition by octanol, like inhibition by sodium, was competitive with calcium. Octanol and sodium together inhibited calcium influx synergistically. At physiological levels of extracellular calcium and sodium, the EC M was 177±37 /ttM for octanol and 48±5 fiM for decanol. These values are threefold to fourfold larger than those reported to cause 50% loss of righting reflex in tadpoles, a measure of their anesthetic effectiveness. We conclude that general anesthetics inhibit Na-Ca exchange at the sarcokmma. We suggest that octanol inhibits like sodium, and the synergism stems from the cooperativity of sodium inhibition at the binding and regulatory sites of the exchanger. Insofar as Na-Ca exchange may regulate inotropy, the inhibition of Na-Ca exchange by general anesthetics could contribute to their negative inotropic effect. (Circulation Research 1989;65:1021-1023)

Age-Dependent Brain Tissue Hydration, Ca Exchange and their Dose- Dependent Ouabain Sensitivity

“…It is well known that anesthetics with different chemical and pharmacological profiles [31][32][33] significantly affect metabolic processes which play an important role in regulation of cell volume [12,34]. Therefore, in present experiments the animals were sharply immobilized by freezing method (dipping their noses into liquid nitrogen for 3-4 sec) and decapitated [35].…”

Alteration of the L‐type calcium current in guinea‐pig single ventricular myocytes by heptaminol hydrochloride

“…An increase in [Ca2+]i has been observed in various cell types during perfusion with membrane active substances (Daniel & Harris, 1988;Davidson et al, 1990). This increase in [Ca2+]i may result from: (1) a release of membrane bound Ca2" (Vassort et al, 1986); (2) an inhibition of Na'-Ca2" exchange mechanism (Michaelis & Michaelis, 1983;Philipson, 1984;Haworth et al, 1989) and of sarcolemmal and intracellular membrane Ca-ATPases (Salama & Scarpa, 1983;Ohnishi et al, 1984). In order to explain their effects on ICa characteristics, Mongo & Vassort (1990) have proposed the participation of an increase in [Ca2+]i as a mechanism of action of n-alkanols and halogenated compounds in addition to those previously described (see Introduction and also Meszaros & Pappano, 1990 (Mentrard et al, 1984;Argibay et al, 1988;Tseng, 1988) (Mentrard et al, 1984).…”

Intercellular calcium signaling via gap junctions in glioma cells.

“…Inhibitors of gap junctional coupling such as octanol, heptanol, halothane, and low pH have been reported to inhibit intercellular Ca : § signaling in Obelia cells (Dunlap et al, 1987), epithelial cells (Sanderson et al, 1990), and Xenopus oocytes (Sandberg et al, 1990). However, each of these inhibitors of gap junctional coupling may have non-specific effects on intracellular Ca 2+ homeostasis (Haworth et al, 1989;Sanderson et al, 1990;Barnes and Bui, 1991;Chang et al, 1991;Mody et al, 1991;Still et al, 1991), raising the possibility that their inhibition of intercellular Ca 2+ signaling may not be due to a direct effect on gap junctions.…”