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

Cardiovasc Res. 2003 Mar 15;57(4):1035-43. doi: 10.1016/s0008-6363(02)00734-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomegaly / etiology
  • Cardiomegaly / metabolism*
  • Cells, Cultured
  • Chronic Disease
  • Dogs
  • Down-Regulation
  • Heart Block / complications
  • Heart Ventricles / metabolism
  • Myocytes, Cardiac / metabolism
  • Patch-Clamp Techniques
  • Sarcoplasmic Reticulum / metabolism
  • Sodium / metabolism*
  • Sodium-Potassium-Exchanging ATPase / metabolism*

Substances

  • Sodium
  • Sodium-Potassium-Exchanging ATPase