Intracellular Na$^+$ concentration is elevated in heart failure but Na/K pump function is unchanged.
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Circulation 105 (21): 2543--2548 (May 2002)

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 approximately 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 V(max) (8.3+/-0.7 versus 8.0+/-0.8 mmol/L/min) or K(m) (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 Ca$^2+$ transient, and prolonged action potential all profoundly affect cellular Ca$^2+$ regulation, promoting greater Ca$^2+$ influx through NCX during action potentials. Notably, the elevated Na$^+$(i) may be critical in limiting the contractile dysfunction observed in HF.
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