The Na⁺/Ca²⁺ exchanger/SR Ca²⁺ ATPase transport capacity regulates the contractility of normal and hypertrophied feline ventricular myocytes

Background: Pressure overload leads to cardiac hypertrophy, which is often followed by heart failure. We tested the hypothesis that depressed contractility in this process results from an imbalance in Ca²⁺ transport by the sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA) and the sarcolemmal Na⁺/Ca²⁺ exchanger (NCX). Methods and Results: Left ventricular (LV) myocytes (n = 79) from 12 normal (N) and 5 hypertrophied (LVH, by aortic banding) feline hearts were studied. Adenoviral gene transfer was used to introduce green fluorescent protein (GFP), SERCA2, and NCX into N and LVH myocytes. Contraction (videomicroscopy) and Ca²⁺ transients (Fluo-3) were measured in steady state and after rest periods of 2 to 120 seconds (rest decay and potentiation). LVH hearts were significantly larger than N (7.1 ± 1.4 versus 4.2 ± 0.2 g/kg). SERCA protein was significantly less abundant in LVH versus N. Steady state contractions and Ca²⁺ transients of LVH-GFP myocytes decayed more slowly and rest decay of contractility was more pronounced compared with N-GFP. Infection of LVH (and N) myocytes with SERCA increased basal contractility and reduced rest decay. Infection of LVH myocytes with NCX almost abolished contraction and in N myocytes reduced contractility and increased rest decay. Conclusion: These findings suggest that an imbalance of Ca²⁺ transport by SERCA and the NCX produces the characteristic contractile abnormalities of hypertrophied cardiac myocytes.