Na(+)/Ca(2+) exchanger expression and function in a rabbit model of myocardial infarction.
BACKGROUND
In general, sarcolemmal Na(+)/Ca(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 approximately 30% was observed. Immunoblot analysis indicated increased NCX protein levels by approximately 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+/-0.05 n=15, P<0.05) compared to sham (1.0+/-0.16, n=15). Sorcin monomer levels were not significantly different (sham: 1.0+/-0.26, LVD: 0.83+/-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(m) at -60 mV decreased NCX-mediated Ca(2+) efflux rates to values comparable to those seen in LVD and increased SR Ca(2+) content and peak systolic [Ca(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(2+) content and Ca(2+) transient amplitude.
Smith
Godfrey L
GL
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK. g.smith@bio.gla.ac.uk
Elliott
Elspeth E B
EE
Kettlewell
Sarah
S
Currie
Susan
S
Quinn
Francis R
FR