Affiliation:
1. 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.
Abstract
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 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
280 articles.
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