Kato K, Shao Q, Elimban V, Lukas A, Dhalla N S
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R2H 2A6.
Am J Physiol. 1998 Sep;275(3):C826-31. doi: 10.1152/ajpcell.1998.275.3.C826.
Oxidative stress during pathological conditions such as ischemia-reperfusion is known to promote the formation of hypochlorous acid (HOCl) in the heart and to result in depression of cardiac sarcolemmal (SL) Na+-K+-ATPase activity. In this study, we examined the direct effects of HOCl on SL Na+-K+-ATPase from porcine heart. HOCl decreased SL Na+-K+-ATPase activity in a concentration- and time-dependent manner. Characterization of Na+-K+-ATPase activity in the presence of different concentrations of MgATP revealed a decrease in the maximal velocity (Vmax) value, without a change in affinity for MgATP on treatment of SL membranes with 0.1 mM HOCl. The Vmax value of Na+-K+-ATPase, when determined in the presence of different concentrations of Na+, was also decreased, but affinity for Na+ was increased when treated with HOCl. Formation of acylphosphate by SL Na+-K+-ATPase was not affected by HOCl. Scatchard plot analysis of [3H]ouabain binding data indicated no significant change in the affinity or maximum binding capacity value for ouabain binding following treatment of SL membranes with HOCl. Western blot analysis of Na+-K+-ATPase subunits in HOCl-treated SL membranes showed a decrease (34 +/- 9% of control) in the beta1-subunit without any change in the alpha1- or alpha2-subunits. These data suggest that the HOCl-induced decrease in SL Na+-K+-ATPase activity may be due to a depression in the beta1-subunit of the enzyme.
