Expression of dihydropyridine receptor (Ca2+ channel) and calsequestrin genes in the myocardium of patients with end-stage heart failure

Toshiyuki Takahashi, Paul D. Allen, Ronald V. Lacro, Andrew R. Marks, A. Robert Dennis, Frederick J. Schoen, William Grossman, James D. Marsh, Seigo Izumo

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

Cytoplasmic free calcium ions (Ca2+) play a central role in excitation-contraction coupling of cardiac muscle. Abnormal Ca2+ handling has been implicated in systolic and diastolic dysfunction in patients with end-stage heart failure. The current study tests the hypothesis that expression of genes encoding proteins regulating myocardial Ca2+ homeostasis is altered in human heart failure. We analyzed RNA isolated from the left ventricular (LV) myocardium of 30 cardiac transplant recipients with end-stage heart failure (HF) and five organ donors (normal control), using cDNA probes specific for the cardiac dihydropyridine (DHP) receptor (the a, subunit of the DHP-sensitive Ca2+ channel) and cardiac calsequestrin of sarcoplasmic reticulum (SR). In addition, abundance of DHP binding sites was assessed by ligand binding techniques (n = 6 each for the patients and normal controls). There was no difference in the level of cardiac calsequestrin mRNA between the HF patients and normal controls. In contrast, the level of mRNA encoding the DHP receptor was decreased by 47% (P < 0.001) in the LV myocardium from the patients with HF compared to the normal controls. The number of DHP binding sites was decreased by 35-48%. As reported previously, expression of the SR Ca2+-ATPase mRNA was also diminished by 50% (P < 0.001) in the HF group. These data suggest that expression of the genes encoding the cardiac DHP receptor and SR Ca2+-ATPase is reduced in the LV myocardium from patients with HF. Altered expression of these genes may be related to abnormal Ca2+ handling in the failing myocardium, contributing to LV systolic and diastolic dysfunction in patients with end-stage heart failure.

Original languageEnglish (US)
Pages (from-to)927-935
Number of pages9
JournalJournal of Clinical Investigation
Volume90
Issue number3
StatePublished - 1992
Externally publishedYes

Fingerprint

Calsequestrin
L-Type Calcium Channels
Myocardium
Heart Failure
Genes
Sarcoplasmic Reticulum
Calcium-Transporting ATPases
Messenger RNA
Binding Sites
Gene Expression
Excitation Contraction Coupling
Homeostasis
Complementary DNA
Tissue Donors
RNA
Ions
Ligands
Calcium

Keywords

  • Calcium atpase
  • Calcium channel
  • Calsequestrin
  • Dihydropyridine receptor
  • Heart failure
  • Human cardiac transplant

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Takahashi, T., Allen, P. D., Lacro, R. V., Marks, A. R., Dennis, A. R., Schoen, F. J., ... Izumo, S. (1992). Expression of dihydropyridine receptor (Ca2+ channel) and calsequestrin genes in the myocardium of patients with end-stage heart failure. Journal of Clinical Investigation, 90(3), 927-935.

Expression of dihydropyridine receptor (Ca2+ channel) and calsequestrin genes in the myocardium of patients with end-stage heart failure. / Takahashi, Toshiyuki; Allen, Paul D.; Lacro, Ronald V.; Marks, Andrew R.; Dennis, A. Robert; Schoen, Frederick J.; Grossman, William; Marsh, James D.; Izumo, Seigo.

In: Journal of Clinical Investigation, Vol. 90, No. 3, 1992, p. 927-935.

Research output: Contribution to journalArticle

Takahashi, T, Allen, PD, Lacro, RV, Marks, AR, Dennis, AR, Schoen, FJ, Grossman, W, Marsh, JD & Izumo, S 1992, 'Expression of dihydropyridine receptor (Ca2+ channel) and calsequestrin genes in the myocardium of patients with end-stage heart failure', Journal of Clinical Investigation, vol. 90, no. 3, pp. 927-935.
Takahashi, Toshiyuki ; Allen, Paul D. ; Lacro, Ronald V. ; Marks, Andrew R. ; Dennis, A. Robert ; Schoen, Frederick J. ; Grossman, William ; Marsh, James D. ; Izumo, Seigo. / Expression of dihydropyridine receptor (Ca2+ channel) and calsequestrin genes in the myocardium of patients with end-stage heart failure. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 3. pp. 927-935.
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