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Cardiovascular Research 2003 57(4):1035-1043; doi:10.1016/S0008-6363(02)00734-4
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Increased Na+ concentration and altered Na/K pump activity in hypertrophied canine ventricular cells

Fons Verdoncka,*, Paul G.A Voldersb, Marc A Vosb and Karin R Sipidoc

aInterdisciplinary Research Center, University of Leuven Campus Kortrijk, E. Sabbelaan 53, B-8500 Kortrijk, Belgium
bDepartment of Cardiology, Academic Hospital Maastricht, Maastricht, The Netherlands
cLaboratory of Experimental Cardiology, University of Leuven, Kortrijk, Belgium

* Corresponding author. Tel.: +32-56-246224; fax: +32-56-246997. fons.verdonck{at}kulak.ac.be

Objective: To investigate whether hypertrophy in the dog with chronic atrioventricular block (CAVB) alters [Na+]i and Na/K-pump function of ventricular myocytes. Methods: We measured the [Na+]i dependence of the Na/K pump current, Ip. This relation was used as a calibration curve for [Na+]i based on Ip. We measured Ip at the time of access and extrapolated [Na+] at the pump sites, i.e. subsarcolemmal [Na+], [Na+]subs, from the calibration curve. Results: The extrapolated [Na+]subs was significantly higher in CAVB (7.9 vs. 3.2 mM in control). The [Na+]i dependence of Ip in CAVB myocytes was shifted to the right (range of [Na+]i: 0–20 mM). In resting cells, the Ip, i.e. steady state Na+ efflux, which matches Na+ influx, was higher in CAVB (0.25±0.02 vs. 0.47±0.06 pA/pF, P<0.05). Maximal Ip density was not different, and DHO sensitivity was not altered. Conclusions: Hypertrophy in CAVB cells is associated with increased [Na+]subs. This results from an increase in Na+ influx, and a decreased sensitivity of Ip for Na+ in the range of [Na+]i studied. There is no evidence for a decrease in total pump capacity or for a functional Na/K-ATPase isoform shift. The rise in Na+ contributes to the contractile adaptation and preservation of sarcoplasmic reticulum Ca2+ content at the low heart rates of the dog with CAVB.

KEYWORDS Calcium (cellular); Hypertrophy; Na/K-pump


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