Expression of skeletal muscle sarcoplasmic reticulum calcium-ATPase is reduced in rats with postinfarction heart failure

Abstract

Objective: To determine whether heart failure in rats is associated with altered expression of the skeletal muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA).

Methods: SERCA protein and mRNA were examined in the soleus muscles of eight female rats with heart failure induced by coronary artery ligation, six weeks after the procedure (mean (SEM) left ventricular end diastolic pressure 20.4 (2.2) mm Hg) and in six sham operated controls by western and northern analyses, respectively.

Results: SERCA-2a isoform protein was reduced by 16% (112 000 (4000) v 134 000 (2000) arbitrary units, p < 0.001), and SERCA-2a messenger RNA was reduced by 59% (0.24 (0. 06) v 0.58 (0.02) arbitrary units, p < 0.001). Although rats with heart failure had smaller muscles (0.54 mg/g v 0.66 mg/g body weight), no difference in locomotor activity was observed.

Conclusions: These results may explain the previously documented abnormalities in calcium handling in skeletal muscle from animals with the same model of congestive heart failure, and could be responsible for the accelerated muscle fatigue characteristic of patients with heart failure.

Figure 1

Immunoblot for SERCA-2a protein, showing two sham operated controls (CON) on the left and two heart failure rats (CHF) on the right.

Figure 2

Mean values for the SERCA protein and mRNA in arbitrary units. Both were significantly reduced in the heart failure rats. CON, control; CHF, chronic heart failure.

Figure 3

Northern blot showing reduced β-MHC and SERCA mRNA signals in the chronic heart failure (CHF) animals compared with controls (CON).