Intracellular Na+ concentration is elevated in heart failure but Na/K pump function is unchanged

Academic Article


  • 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.
  • Authors

    Published In

  • Circulation  Journal
  • Digital Object Identifier (doi)

    Author List

  • Despa S; Islam MA; Weber CR; Pogwizd SM; Bers DM
  • Start Page

  • 2543
  • End Page

  • 2548
  • Volume

  • 105
  • Issue

  • 21