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

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, I-p. This relation was used as a calibration curve for [Na+](i) based on I-p. We measured I-p 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 I-p in CAVB myocytes was shifted to the right (range of [Na+](i): 0-20 mM). In resting cells, the I-p, 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 I-p 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 I-p 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. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.