Effects of potassium modulations on digoxin - induced inhibition of porcine cerebral cortex Na+/K+-ATPase
2003
Krstic, D. (University of Belgrade, Belgrade (Serbia and Montenegro). School of Medicine, Institute of Chemistry)
The purpose of this work was to establish the in vitro influence of K+ ions in the concentration range from 2 mM to 500 mM on digoxin - induced inhibition of the porcine cerebral cortex Na+/K+-ATPase activity. Furthermore, we examined the possibility of prevention and recovery of digoxin - induced inhibition of Na+/K+-ATPase activity by elevated potassium concentrations. The response of the enzymatic activity in the presence of various K+ concentration to digoxin was biphasic, thereby, indicating the existence of two Na+/K+-ATPase isoforms, differing in the affinity towards the tested drug. An adequate computer programme was designed to calculate IC50 values for digoxin - induced inhibition of both isoforms. The IC50 values for high/low isoforms 2.77 x 10E-6 M / 8.56 x 10E-5 M and 8.06 x 10E-7 M/ 1.87 x 10E-5 M were obtained in the presence of 20 mM and 2 mM K+ in the medium assay, respectively. The preincubation in the presence of 50 - 500m M K+ in the medium assay prior to Na+/K+-ATPase exposure to digoxin did not prevent the inhibition. The adding of 200 mM K+ into the medium assay after 10 minutes exposure of Na+/K+-ATPase to digoxin, instigated only 30 percent recovery of relative enzymatic activity. Kinetic analysis in the absence and the presence of digoxin indicated that digoxin is uncompetitive inhibitor of the high affinity enzyme isoform.
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