Na(+)-K(+)-ATPase alpha(2)-isoform expression in guinea pig hearts during transition from compensation to decompensation.
Disturbance in ionic gradient across sarcolemma may lead to arrhythmias. Because Na(+)-K(+)-ATPase regulates intracellular Na(+) and K(+) concentrations, and therefore intracellular Ca(2+) concentration homeostasis, our aim was to determine whether changes in the Na(+)-K(+)-ATPase alpha-isoforms in guinea pigs during transition from compensated (CLVH) to decompensated left ventricular hypertrophy (DLVH) were concomitant with arrhythmias. After 12- and 20-mo aortic stenosis, CLVH and DLVH were characterized by increased mean arterial pressure (30% and 52.7%, respectively). DLVH differed from CLVH by significantly increased end-diastolic pressure (34%), decreased sarco(endo)plasmic reticulum Ca(2+)-ATPase (-75%), and increased Na(+)/Ca(2+) exchanger (25%) mRNA levels and by the occurrence of ventricular arrhythmias. The alpha-isoform (mRNA and protein levels) was significantly lower in DLVH (2.2 +/- 0.2- and 1. 4 +/- 0.15-fold, respectively, vs. control) than in CLVH (3.5 +/- 0. 4- and 2.2 +/- 0.13-fold, respectively) and was present in sarcolemma and T tubules. Changes in the levels of alpha(1)- and alpha(3)-isoform in CLVH and DLVH appear physiologically irrelevant. We suggest that the increased level of alpha(2)-isoform in CLVH may participate in compensation, whereas its relative decrease in DLVH may enhance decompensation and arrhythmias.
Trouve
P
P
Institut National de la Santé et de la Recherche Médicale, Unité 127, Institut Fédératif de Recherche Circulation Lariboisière, Université Denis Diderot, 75475 Paris, France.
Carre
F
F
Belikova
I
I
Leclercq
C
C
Dakhli
T
T
Soufir
L
L
Coquard
I
I
Ramirez-Gil
J
J
Charlemagne
D
D
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006333:Heart Failure; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000503:physiopathology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D012333:RNA, Messenger; D000254:Sodium-Potassium-Exchanging ATPase