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(Circulation. 2001;103:2739.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Increased Expression of Isoform 1 of the Sarcoplasmic Reticulum Ca²⁺-Release Channel in Failing Human Heart

Götz Münch, MD; Birgit Bölck, PhD; Alina Sugaru, MS; Klara Brixius, PhD; Wilhelm Bloch, PhD; Robert H.G. Schwinger, MD

From the Laboratory of Muscle Research and Molecular Cardiology, Klinik III für Innere Medizin (G.M., B.B., A.S., K.B., R.H.G.S.) and Department of Anatomy (W.B.), University of Cologne, Cologne, Germany.

Correspondence to Priv-Doz Dr med Robert H.G. Schwinger, Klinik III für Innere Medizin, University of Cologne, Joseph-Stelzmann-Straße 9, 50924 Cologne, Germany. E-mail Robert.Schwinger{at}medizin.uni-koeln.de

Background—The sarcoplasmic reticulum (SR) Ca²⁺-release channel plays a key role in the excitation-contraction coupling of cardiac myocytes. Because respective alterations have been reported in human heart failure, we investigated isoform expression of the SR Ca²⁺-release channel in human hearts from patients with terminal heart failure (dilated cardiomyopathy [DCM], n=8) and nonfailing organ donors (NF, n=8).

Methods and Results—Expression of mRNA of SR Ca²⁺-release channel isoforms in isolated human cardiomyocytes and myocardial tissue was analyzed by reverse-transcription polymerase chain reaction. Protein expression was quantified in myocardial tissue with [³H]-ryanodine binding and with Western blots, expressed as densitometric units per microgram of protein (DU), and cellular localization was visualized with immunohistochemistry. We found mRNA expression of isoforms 1, 2, and 3 in cardiomyocytes and myocardial tissue both in NF and DCM. Total SR Ca²⁺-release channel protein expression in NF (B_max 2.16±0.43 pmol/mg protein) and in DCM (B_max 2.33±0.22 pmol/mg protein) myocardium was unchanged. Expression of isoform 1 of the SR Ca²⁺-release channel was significantly (P=0.0037) increased in DCM myocardium (NF 1.97±0.25 versus DCM 3.37±0.31 DU), whereas protein expression of isoform 2 (NF 14.62±0.87 versus DCM 13.52±0.43 DU) and isoform 3 (NF 1.39±0.13 versus DCM 1.35±0.19 DU) was unchanged. All 3 isoforms of the protein could be localized in human ventricular myocytes with fluorescence immunohistochemistry.

Conclusions—All 3 isoforms of the SR Ca²⁺-release channel were determined in human ventricular cardiomyocytes. Increased expression of isoform 1 of the SR Ca²⁺-release channel could contribute to impaired excitation-contraction coupling in human heart failure.

Key Words: sarcoplasmic reticulum • heart failure • calcium • receptors

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