Myocardial infarction causes increased expression but decreased activity of the myocardial Na⁺-Ca²⁺ exchanger in the rabbit

Quinn, F.R., Currie, S., Duncan, A.M., Miller, S., Sayeed, R., Cobbe, S.M. and Smith, G.L. (2003) Myocardial infarction causes increased expression but decreased activity of the myocardial Na⁺-Ca²⁺ exchanger in the rabbit. Journal of Physiology, 553(1), pp. 229-242. (doi: 10.1113/jphysiol.2003.050716)

Abstract

Na⁺-Ca²⁺ exchanger (NCX) protein levels and activity were measured in myocardium from the basal region of the left ventricle of rabbit hearts with significant left ventricular dysfunction (LVD), 8-9 weeks after an apical infarction. NCX protein abundance was higher in the tissue homogenates (121 +/- 11 %) and purified membrane fractions (143 ± 12 %) in the LVD compared to the sham-operated (sham) group. NCX mRNA was also higher in the LVD group (126 %). Lower NCX protein expression was observed in the membrane fractions from the epicardium compared to the endocardium in both the sham and LVD groups. Transmembrane currents were recorded in isolated cardiomyocytes by single-electrode voltage clamp; [Ca²⁺](i) was measured using Fura-2. Rapid application of 10 mmol l^-1 caffeine was used to induce Ca²⁺ release from the sarcoplasmic reticulum. The subsequent NCX-mediated Ca²⁺ efflux rate constant was lower (70 % of sham) in the LVD group. NCX currents were measured in cardiomyocytes dialysed with 250 nm Ca²⁺ (50 mmol l^-1 EGTA). A lower NCX current (75 % of sham) was observed in the LVD group. Lower NCX activity was also observed in cardiomyocytes isolated from the epicardium compared to the endocardium; a transmural difference that was also seen in the LVD group. Reduced activity despite increased protein expression may result from reduced Ca²⁺ sensitivity of the allosteric regulation of NCX. However, measurements indicated increased Ca²⁺ sensitivity in the LVD group. Cardiomyocytes from LVD hearts displayed a marked reduction in the transverse tubule area (59 % of sham) and the surface area/volume ratio (80 % of sham). Disrupted transverse tubule structure may contribute to the decrease in NCX activity despite increased protein expression in LVD.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Professor Godfrey and Miller, Mr Stephen and Cobbe, Professor Stuart and Currie, Mrs Shona
• Authors: Quinn, F.R., Currie, S., Duncan, A.M., Miller, S., Sayeed, R., Cobbe, S.M., and Smith, G.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Journal of Physiology
• ISSN: 0022-3751
• ISSN (Online): 1469-7793
• Published Online: 29 August 2003