Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with end-stage heart failure caused by ischemic versus dilated cardiomyopathy

Anne Marie Brillantes, Paul Allen, Toshiyuki Takahashi, Seigo Izumo, Andrew R. Marks

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

The molecular basis for the systolic and diastolic dysfunction characteristic of end-stage heart failure in humans remains poorly understood. It has been proposed that both abnormal calcium handling and defects in the contractile apparatus may contribute to the myocardial dysfunction. Two channels, the calcium release channel (CRC) or ryanodine receptor of the sarcoplasmic reticulum (SR), and the slow calcium channel or dihydropyridine receptor (DHPR) of the transverse tubule, play key roles in regulating intracellular calcium concentration and in excitation-contraction (E-C) coupling in the heart. The DHPR serves as the voltage sensor and plasma membrane calcium channel resulting in activation of the CRC during E-C coupling in heart muscle. In this study, we investigated the levels of CRC expression in several forms of end-stage heart failure in humans. A cardiac CRC cDNA was cloned from rabbit and used as a probe for Northern blot analyses to determine mRNA levels in the left ventricles of normal (n=4) and cardiomyopathic (n=34) human hearts from patients undergoing cardiac transplantation. Compared with normal patients, patients with ischemic cardiomyopathy (n=18) showed a 28% decrease in CRC mRNA levels (p<0.025) and patients with idiopathic dilated cardiomyopathy (n=14) a nonsignificant 12% increase. In these same hearts, α-actin levels were unchanged in end-stage heart failure, as has been previously reported. This is the first report indicating that the expression of the CRC mRNA is abnormal in end-stage human heart failure. The decreased expression of the CRC found specifically in patients with ischemic myopathy (but not idiopathic dilated cardiomyopathy) may, in part, explain differences in calcium handling and response to therapy observed among patients with different forms of cardiomyopathy. Decreased CRC expression could be related to abnormal contractile function in cardiomyopathic muscle resulting from ischemic insult.

Original languageEnglish (US)
Pages (from-to)18-26
Number of pages9
JournalCirculation Research
Volume71
Issue number1
StatePublished - Jul 1992
Externally publishedYes

Keywords

  • Calcium release channel
  • Idiopathic dilated cardiomyopathy
  • Ischemic cardiomyopathy
  • mRNA
  • Ryanodine receptor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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