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Ouabain binding and inotropy in acute potassium depletion in guinea pigs
Abstract:
In hypokalaemia the incidence of cardiac toxicity with digitalis is increased, possibly through changes in the affinity or capacity of the digitalis receptor in the heart. Previous studies have reported an increased ouabain binding capacity or Na+-K+ ATPase activity after hypokalaemia in human erythrocytes and rabbit and guinea pig hearts and no change or decreases in rabbit or rat skeletal muscles with no changes in ouabain affinity. The present study determined (a) the effect of potassium on 3H-ouabain binding to normokalaemic guinea pig cardiac cell membranes, (b) the effect of acute hypokalaemia induced by a potassium deficient diet for 14-18 days in guinea pigs on 3H-ouabain binding to erythrocytes and cardiac and skeletal muscle homogenates, and (c) ouabain induced inotropy in isolated contracting guinea pig left atria, right ventricular papillary muscles, and soleus muscle strips from normokalaemic and hypokalaemic guinea pigs. 3H-ouabain binds to cardiac cell membranes in the presence of magnesium and inorganic phosphate with an affinity (KD value) of 1.13 X 10(-7) mol X litre-1. Potassium decreased this affinity without changing the binding capacity. Erythrocytes and heart muscle homogenates showed the same affinity as cardiac cell membranes, whereas soleus muscle homogenates had a higher affinity for ouabain (KD 5.1 X 10(-8) mol X litre-1). After hypokalaemia, the ouabain affinity did not change in any tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Hypokalemia, or low potassium, does not alter ouabain affinity in guinea pig tissues. This suggests that changes in digitalis receptor binding capacity, not affinity, may explain increased cardiac toxicity during hypokalemia.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Biochemistry
Background:
- Hypokalemia increases cardiac toxicity risk with digitalis drugs.
- Previous studies suggest altered digitalis receptor binding capacity or Na+-K+ ATPase activity in hypokalemia.
- The role of ouabain affinity in hypokalemia-induced digitalis toxicity remains unclear.
Purpose of the Study:
- To investigate the effect of potassium on 3H-ouabain binding to guinea pig cardiac membranes.
- To determine the impact of acute hypokalemia on 3H-ouabain binding in various guinea pig tissues.
- To assess ouabain-induced inotropy in cardiac and skeletal muscles from normokalemic and hypokalemic guinea pigs.
Main Methods:
- Studied 3H-ouabain binding to guinea pig cardiac cell membranes with varying potassium levels.
- Induced acute hypokalemia in guinea pigs via a potassium-deficient diet.
- Measured 3H-ouabain binding in erythrocytes, cardiac, and skeletal muscle homogenates.
- Assessed ouabain-induced inotropy in isolated cardiac and skeletal muscle preparations.
Main Results:
- Potassium decreased 3H-ouabain binding affinity to cardiac membranes without altering capacity.
- Erythrocytes and heart muscle showed similar ouabain affinity; soleus muscle had higher affinity.
- Hypokalemia did not change ouabain affinity in erythrocytes, cardiac, or skeletal muscle homogenates.
- Ouabain-induced inotropy results were not detailed in the truncated abstract.
Conclusions:
- Potassium concentration influences ouabain binding affinity to cardiac membranes.
- Hypokalemia does not alter ouabain affinity in guinea pig cardiac or skeletal muscles.
- Findings suggest that altered digitalis receptor binding capacity, rather than affinity, may underlie increased cardiac toxicity in hypokalemia.