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

F R Quinn, S Currie, A M Duncan, S Miller, R Sayeed, S M Cobbe, G L Smith

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)229-242
Number of pages14
JournalJournal of Physiology
Volume553
Issue number1
DOIs
Publication statusPublished - Nov 2003

Fingerprint

Left Ventricular Dysfunction
Myocardial Infarction
Rabbits
Cardiac Myocytes
Endocardium
Pericardium
Proteins
Allosteric Regulation
Membranes
Fura-2
Egtazic Acid
Sarcoplasmic Reticulum
Caffeine
Infarction
Heart Ventricles
Myocardium
Electrodes
Messenger RNA

Keywords

  • myocardium
  • heart failure
  • myocardial infarction
  • cardiomyocytes

Cite this

Quinn, F R ; Currie, S ; Duncan, A M ; Miller, S ; Sayeed, R ; Cobbe, S M ; Smith, G L. / Myocardial infarction causes increased expression but decreased activity of the myocardial Na+-Ca2+ exchanger in the rabbit. In: Journal of Physiology. 2003 ; Vol. 553, No. 1. pp. 229-242.
@article{c059d8c4bcdb4fa6900bd44d24438a91,
title = "Myocardial infarction causes increased expression but decreased activity of the myocardial Na+-Ca2+ exchanger in the rabbit",
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.",
keywords = "myocardium, heart failure, myocardial infarction, cardiomyocytes",
author = "Quinn, {F R} and S Currie and Duncan, {A M} and S Miller and R Sayeed and Cobbe, {S M} and Smith, {G L}",
year = "2003",
month = "11",
doi = "10.1113/jphysiol.2003.050716",
language = "English",
volume = "553",
pages = "229--242",
journal = "Journal of Physiology",
issn = "0022-3751",
number = "1",

}

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; Smith, G L.

In: Journal of Physiology, Vol. 553, No. 1, 11.2003, p. 229-242.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Myocardial infarction causes increased expression but decreased activity of the myocardial Na+-Ca2+ exchanger in the rabbit

AU - Quinn, F R

AU - Currie, S

AU - Duncan, A M

AU - Miller, S

AU - Sayeed, R

AU - Cobbe, S M

AU - Smith, G L

PY - 2003/11

Y1 - 2003/11

N2 - 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.

AB - 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.

KW - myocardium

KW - heart failure

KW - myocardial infarction

KW - cardiomyocytes

U2 - 10.1113/jphysiol.2003.050716

DO - 10.1113/jphysiol.2003.050716

M3 - Article

C2 - 12949221

VL - 553

SP - 229

EP - 242

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 1

ER -