Na+/Ca2+ Exchanger Expression and Function in a Rabbit Model of Myocardial Infarction

Smith, G.L. , Elliott, E.B., Kettlewell, S., Currie, S. and Quinn, F.R. (2006) Na+/Ca2+ Exchanger Expression and Function in a Rabbit Model of Myocardial Infarction. Journal of Cardiovascular Electrophysiology, 17(s1), S57-S63. (doi:10.1111/j.1540-8167.2006.00384.x)

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Abstract

Introduction: In general, sarcolemmal Na+/Ca2+ 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 ∼30% was observed. Immunoblot analysis indicated increased NCX protein levels by ∼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 Em at −60 mV decreased NCX-mediated Ca2+ efflux rates to values comparable to those seen in LVD and increased SR Ca2+ content and peak systolic [Ca2+] 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 Ca2+ content and Ca2+ transient amplitude.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and Kettlewell, Dr Sarah and Elliott, Dr Elspeth
Authors: Smith, G.L., Elliott, E.B., Kettlewell, S., Currie, S., and Quinn, F.R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences
Journal Name:Journal of Cardiovascular Electrophysiology
Publisher:Blackwell
ISSN:1540-8167

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