Na super(+)-Ca super(2+) Exchanger Expression and Function in a Rabbit Model of Myocardial Infarction

Introduction: In general, sarcolemmal Na super(+)-Ca super(2+) exchanger (NCX) protein and activity is increased in hearts with ventricular dysfunction. However, in a subset of studies, reduced activity of NCX has been reported. Left ventricular dysfunction (LVD) was induced in the rabbit eight weeks after an apical myocardial infarction. Methods: Using single microelectrode voltage clamp to assess the NCX activity in isolated ventricular cells, a decrease in NCX activity by similar to 30% was observed. Immunoblot analysis indicated increased NCX protein levels by similar to 20% in the LVD group. The cause of this paradox is unknown. Overexpression of the protein sorcin increased the activity of NCX without affecting NCX protein levels. Results: Sorcin protein (dimer) levels were significantly lower in the LVD group (0.67 plus or minus 0.05 n = 15, P < 0.05) compared to sham (1.0 plus or minus 0.16, n = 15). Sorcin monomer levels were not significantly different (sham: 1.0 plus or minus 0.26, LVD: 0.83 plus or minus 0.13). Mathematical modeling of NCX suggests that a reduction of NCX activity during diastole to that in LVD could be achieved by holding the diastolic membrane potential at -60 mV instead of -80 mV. Holding E sub(m) at -60 mV decreased NCX-mediated Ca super(2+) efflux rates to values comparable to those seen in LVD and increased SR Ca super(2+) content and peak systolic [Ca super(2+)] in sham and LVD cardiomyocytes. Conclusions: In conclusion, reduced sorcin expression may be linked to the lower NCX activity in the rabbit model of LVD. Reduced NCX activity during diastole increases SR Ca super(2+) content and Ca super(2+) transient amplitude.