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.
Kjeldsen
K
K
Department of Medicine (Division of Cardiology), Rigshospitalet, University of Copenhagen, School of Medicine, Denmark.
Grøn
P
P
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