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.
Verdonck
Fons
F
Interdisciplinary Research Center, University of Leuven Campus Kortrijk, E. Sabbelaan 53, B-8500, Kortrijk, Belgium. fons.verdonck@kulak.ac.be <fons.verdonck@kulak.ac.be>
Volders
Paul G A
PG
Vos
Marc A
MA
Sipido
Karin R
KR
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism*; D002478:Cells, Cultured; D002908:Chronic Disease; D004285:Dogs; D015536:Down-Regulation; D006327:Heart Block / Q000150:complications; D006352:Heart Ventricles / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase