Circulation. 2002;105:2543-2548
Published online before print May 13, 2002, doi: 10.1161/01.CIR.0000016701.85760.97
Published online before print May 13, 2002, doi: 10.1161/01.CIR.0000016701.85760.97
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(Circulation. 2002;105:2543.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Intracellular Na+ Concentration Is Elevated in Heart Failure But Na/K Pump Function Is Unchanged
From the Department of Physiology (S.D., C.R.W., D.M.B.), Loyola University Chicago, Maywood, Ill; and the Department of Medicine (M.A.I., S.M.P.), University of Illinois at Chicago.
Correspondence to Dr Donald M. Bers, Department of Physiology, Loyola University Chicago, 2160 S First Ave, Maywood, IL 60153. E-mail dbers{at}lumc.edu
Background— Intracellular sodium concentration ([Na+]i) modulates cardiac contractile and electrical activity through Na/Ca exchange (NCX). Upregulation of NCX in heart failure (HF) may magnify the functional impact of altered [Na+]i.
Methods and Results— We measured [Na+]i by using sodium binding benzofuran isophthalate in control and HF rabbit ventricular myocytes (HF induced by aortic insufficiency and constriction). Resting [Na+]i was 9.7±0.7 versus 6.6±0.5 mmol/L in HF versus control. In both cases, [Na+]i increased by 
2 mmol/L when myocytes were stimulated (0.5 to 3 Hz). To identify the mechanisms responsible for [Na+]i elevation in HF, we measured the [Na+]i dependence of Na/K pump–mediated Na+ extrusion. There was no difference in Vmax (8.3±0.7 versus 8.0±0.8 mmol/L/min) or Km (9.2±1.0 versus 9.9±0.8 mmol/L in HF and control, respectively). Therefore, at measured [Na+]i levels, the Na/K pump rate is actually higher in HF. However, resting Na+ influx was twice as high in HF versus control (2.3±0.3 versus 1.1±0.2 mmol/L/min), primarily the result of a tetrodotoxin-sensitive pathway.
Conclusions— Myocyte [Na+]i is elevated in HF as a result of higher diastolic Na+ influx (with unaltered Na/K-ATPase characteristics). In HF, the combined increased [Na+]i, decreased Ca2+ transient, and prolonged action potential all profoundly affect cellular Ca2+ regulation, promoting greater Ca2+ influx through NCX during action potentials. Notably, the elevated [Na+]i may be critical in limiting the contractile dysfunction observed in HF.
Key Words: sodium • heart failure • calcium
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