Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with end-stage heart failure caused by ischemic versus dilated cardiomyopathy.
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 less than 0.025) and patients with idiopathic dilated cardiomyopathy (n = 14) a nonsignificant 12% increase. In these same hearts, alpha-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Brillantes
A M
AM
Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029.
Allen
P
P
Takahashi
T
T
Izumo
S
S
Marks
A R
AR
D000328:Adult; D001483:Base Sequence; D015220:Calcium Channels / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000235:genetics; D002303:Cardiac Output, Low / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000150:complications*; D003327:Coronary Disease / Q000150:complications*; D004247:DNA; D015342:DNA Probes / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D015220:Calcium Channels; D015342:DNA Probes; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; D004247:DNA; D000252:Calcium-Transporting ATPases