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.