Kinetics of Cu2+ inhibition of Na+K+-ATPase

Abstract

The interaction o f C u 2+ with enzymatic activity o f rabbit kidney N a + /K +-ATPase was studied in media w ith buf fered, defined free C u 2+ levels. The IC 50-values are 0.1 ¿imol/1 for N a*/K +-ATPase and 1 ¿¿mo 1/1 for K +-pNPPase. Dithiothreitol (DTT) reverses the inhibitory effect o f C u2+ in vitro. C u 2+ exerts non-competitive effects on the enzyme with respect to N a +, K +, ATP or pNPP, but has a mixed-type inhibitory effect with respect to M g 2+. It is concluded that the appreciation o f the inhibitory effect o f C u 2+ on this enzyme requires carefully composed assay media that in clude a buffer for C u 24', and that the IC 50-values calculated according to this model indicate that C u 2+ may be more toxic than previously anticipated.

Cu2+ and acute thermal stress induce protective eventsviathe p38-MAPK signalling pathway in the perfusedRana ridibundaheart

“…In addition, copper has been proposed to inhibit the activity of the antiporter Na + /K + -ATPase (Li et al, 1996;Handy et al, 2002). In the amphibian heart, inhibition of Na + /K + -ATPase by ouabain also induces a strong activation of p38-MAPK , indicating that copper could stimulate the kinase through this mechanism.…”

Sodium-sensitive and -insensitive copper accumulation by isolated intestinal cells of rainbow troutOncorhynchus mykiss

“…The decrease in cell Na + content at low external pH in the presence of high Cu o can be explained by: (i) reduced competitive binding of external Na + to the cell in the presence of external Cu 2+ with H + (Handy and Eddy, 1991;Handy et al, 2002), and (ii) reversal of the Na + /H + exchanger during external acidification (Ellis and Macleod, 1985), which is stimulated by Cu o (Kramhøft et al, 1988). Cu-dependent inhibition of Na + K + -ATPase (Li et al, 1996) (Skou, 1983), suggesting the Na + /H + exchanger is more critical for controlling cell Na + content in conditions of high Cu o and low external pH. Alternative hypotheses to pH o -dependent Cu accumulation via Ctr1, such as Cu uptake on other pH-sensitive divalent ion transporters, or increased Cu entry into the cell as an artefact of Cu speciation at low pH, are excluded.…”

Metallothionein induction and bioaccumulation kinetics of Cd and Ag in the marine fish Terapon jarbua challenged with dietary or waterborne Ag and Cu

“…Both responses can bar the entry of toxicants and prevent them from reaching the blood stream. There have been many studies on the disruption of osmotic and ionic functions of fish gills exposed to Cu as a result of direct Cu inhibition on Na + /K + ATPase (Li et al 1996). Since Na + /K + ATPase is mainly responsible for Ag gill uptake by fish (Buhl & Hamilton 1990), the reduced Ag uptake may be caused by the decreasing Na + /K + ATPase activity as a result of Cu exposure.…”