Na+/Ca2+ exchanger expression and function in a rabbit model of myocardial infarction

G.L. Smith, E.E.B. Elliot, S. Kettlewell, S. Currie, F.R. Quinn

Research output: Contribution to journalArticle

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Abstract

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. 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. 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. 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.
LanguageEnglish
PagesS57-S63
JournalJournal of Cardiovascular Electrophysiology
Volume17
Issue number1
DOIs
Publication statusPublished - 2006

Fingerprint

Left Ventricular Dysfunction
Myocardial Infarction
Rabbits
Diastole
Proteins
Ventricular Dysfunction
Microelectrodes
Cardiac Myocytes
Membrane Potentials

Keywords

  • sorcin
  • heart failure
  • Na/Ca exchanger
  • biomedical sciences
  • pharmacology
  • myocardial infarction

Cite this

Smith, G.L. ; Elliot, E.E.B. ; Kettlewell, S. ; Currie, S. ; Quinn, F.R. / Na+/Ca2+ exchanger expression and function in a rabbit model of myocardial infarction. In: Journal of Cardiovascular Electrophysiology. 2006 ; Vol. 17, No. 1. pp. S57-S63.
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Na+/Ca2+ exchanger expression and function in a rabbit model of myocardial infarction. / Smith, G.L.; Elliot, E.E.B.; Kettlewell, S.; Currie, S.; Quinn, F.R.

In: Journal of Cardiovascular Electrophysiology, Vol. 17, No. 1, 2006, p. S57-S63.

Research output: Contribution to journalArticle

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T1 - Na+/Ca2+ exchanger expression and function in a rabbit model of myocardial infarction

AU - Smith, G.L.

AU - Elliot, E.E.B.

AU - Kettlewell, S.

AU - Currie, S.

AU - Quinn, F.R.

PY - 2006

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AB - 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. 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. 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. 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.

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KW - heart failure

KW - Na/Ca exchanger

KW - biomedical sciences

KW - pharmacology

KW - myocardial infarction

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U2 - 10.1111/j.1540-8167.2006.00384.x

DO - 10.1111/j.1540-8167.2006.00384.x

M3 - Article

VL - 17

SP - S57-S63

JO - Journal of Cardiovascular Electrophysiology

T2 - Journal of Cardiovascular Electrophysiology

JF - Journal of Cardiovascular Electrophysiology

SN - 1045-3873

IS - 1

ER -