Age-dependent change in myocardial cardiac glycoside receptor (Na,K-pump) concentration in children.
Myocardial Na,K-ATPase concentration was quantified in 18 0-8-year-old human subjects by vanadate-facilitated 3H-ouabain binding to intact samples of the left ventricle of the heart obtained at autopsy. Within the first 6 months of life, the Na,K-ATPase concentration showed a rapid decrease. The mean value in the age range from birth to 6 months was 1.6 times the mean value obtained in the age range 6 months to 8 years. The mean values +/- SEM were 1,076 +/- 57 (n = 10) and 671 +/- 28 (n = 8) (p less than 0.001) pmol/g wet weight, respectively. The highest value [1,433 +/- 56 pmol/g wet weight (n = 5)] was found in a 3-month-old child and the lowest value [545 +/- 22 pmol/g wet weight (n = 5)] in an 8-year-old. Evaluation of 3H-ouabain-binding kinetics showed no age-dependent variations. The total amount of Na,K-ATPase found in the heart was approximately 30 and 80 nmol within the first 3 years of life and at 8 years, respectively. The age-dependent change in myocardial Na,K-ATPase concentration can be ascribed to variation in the ratio between the amount of Na,K-ATPase and muscle mass during development. Since myocardial Na,K-ATPase is the receptor for cardiac glycosides, the present results may in part explain the clinical observation that cardiac glycoside sensitivity and toxicity change in young age.
Department of Medicine (Division of Cardiology), Rigshospitalet, University of Copenhagen, School of Medicine, Denmark.
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D000375:Aging / Q000378:metabolism*; D002301:Cardiac Glycosides / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006321:Heart / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009929:Organ Size; D010042:Ouabain / Q000378:metabolism / Q000493:pharmacokinetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D002301:Cardiac Glycosides; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase