The influence of potassium ion (K+) on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase |
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Authors: | Danijela Krstić Nenad Tomić Katarina Krinulović Vesna Vasić |
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Affiliation: | 1. Institute of Chemistry, School of Medicine, University of Belgrade, Belgrade, Serbia &2. Montenegro;3. School of Medicine, University of Belgrade, Belgrade, Serbia &4. Vin?a Institute of Nuclear Sciences, Belgrade, Serbia & |
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Abstract: | The in vitro influence of potassium ion modulations, in the concentration range 2 mM–500 mM, on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase activity was studied. The response of enzymatic activity in the presence of various K+ concentrations to digoxin was biphasic, thereby, indicating the existence of two Na+/K+-ATPase isoforms, differing in the affinity towards the tested drug. Both isoforms showed higher sensitivity to digoxin in the presence of K+ ions below 20 mM in the medium assay. The IC50 values for high/low isoforms 2.77 × 10? 6 M / 8.56 × 10? 5 M and 7.06 × 10? 7 M /1.87 × 10? 5 M were obtained in the presence of optimal (20 mM) and 2 mM K+, respectively. However, preincubation in the presence of elevated K+ concentration (50 – 500 mM) in the medium assay prior to Na+/K+-ATPase exposure to digoxin did not prevent the inhibition, i.e. IC50 values for both isoforms was the same as in the presence of the optimal K+ concentration. On the contrary, addition of 200 mM K+ into the medium assay after 10 minutes exposure of Na+/K+-ATPase to digoxin, showed a time-dependent recovery effect on the inhibited enzymatic activity. Kinetic analysis showed that digoxin inhibited Na+/K+-ATPase by reducing maximum enzymatic velocity (Vmax) and Km, implying an uncompetitive mode of interaction. |
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Keywords: | Na+/K+-ATPase digoxin inhibition potassium modulations |
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