The molecular basis of human heart failure is unknown. Alterations in calcium homeostasis have been observed in failing human heart muscles. Intracellular calcium-release channels regulate the calcium flux required for muscle contraction. Two forms of intracellular calcium-release channels are expressed in the heart: the ryanodine receptor (RyR) and the inositol 1,4,5-trisphosphate receptor (IP3R). In the present study we showed that these two cardiac intracellular calcium release channels were regulated in opposite directions in failing human hearts. In the left ventricle, RyR mRNA levels were decreased by 31% (P < 0.025) whereas IP3R mRNA levels were increased by 123% (P < 0.005). In situ hybridization localized both RyR and IP3R mRNAs to human cardiac myocytes. The relative amounts of IP3 binding sites increased approximately 40% compared with ryanodine binding sites in the failing heart. RyR down-regulation could contribute to impaired contractility; IP3R up regulation may be a compensatory response providing an alternative pathway for mobilizing intracellular calcium release, possibly contributing to the increased diastolic tone associated with heart failure and the hypertrophic response of failing myocardium.
L O Go, M C Moschella, J Watras, K K Handa, B S Fyfe, A R Marks
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Journal of Cardiac Failure | 2003 |
Stanniocalcin-1 is a naturally occurring L-channel inhibitor in cardiomyocytes: relevance to human heart failure
D Sheikh-Hamad, R Bick, GY Wu, BM Christensen, P Razeghi, B Poindexter, H Taegtmeyer, A Wamsley, R Padda, M Entman, S Nielsen, K Youker |
American journal of physiology. Heart and circulatory physiology | 2003 |
Cardiac Remodeling and Failure
PK Singal, IM Dixon, LA Kirshenbaum, NS Dhalla |
2003 | |
Cardiac Repolarization
I Gussak, C Antzelevitch, SC Hammill, WK Shen, P Bjerregaard |
2003 | |
Heart Failure, Oxidative Stress, and Ion Channel Modulation
G Choudhary, SC Dudley |
Congestive Heart Failure | 2002 |
Three-dimensional structure of the type 1 inositol 1,4,5-trisphosphate receptor at 24 A resolution
QX Jiang, EC Thrower, DW Chester, BE Ehrlich, FJ Sigworth |
The EMBO Journal | 2002 |
Ca2+ waves require sequential activation of inositol trisphosphate receptors and ryanodine receptors in pancreatic acini
MF Leite, AD Burgstahler, MH Nathanson |
Gastroenterology | 2002 |
Calcium sparks in human ventricular cardiomyocytes from patients with terminal heart failure
M Lindner, MC Brandt, H Sauer, J Hescheler, T Böhle, DJ Beuckelmann |
Cell Calcium | 2002 |
The role of inositol 1,4,5-trisphosphate receptors in Ca 2+ signalling and the generation of arrhythmias in rat atrial myocytes
L Mackenzie, MD Bootman, M Laine, MJ Berridge, A Holmes, WH Li, P Lipp |
The Journal of Physiology | 2002 |
Calcium Cycling in Congestive Heart Failure
G Hasenfuss, B Pieske |
Journal of Molecular and Cellular Cardiology | 2002 |
Calcium Cycling, Historic Overview and Perspectives. Role for Autonomic Nervous System Regulation
NN Petrashevskaya, SE Koch, I Bodi, A Schwartz |
Journal of Molecular and Cellular Cardiology | 2002 |
Exercise training normalizes altered calcium-handling proteins during development of heart failure
L Lu, DF Mei, AG Gu, S Wang, B Lentzner, DE Gutstein, D Zwas, S Homma, GH Yi, J Wang |
Journal of applied physiology | 2002 |
Differential Mechanisms of Ca2+ Release from Vascular Smooth Muscle Cell Microsomes
AN Yusufi, J Cheng, MA Thompson, JC Burnett, JP Grande |
Experimental biology and medicine (Maywood, N.J.) | 2002 |
Electrical and structural remodeling of the failing ventricle
AA Armoundas, R Wu, G Juang, E Marbán, GF Tomaselli |
Pharmacology & Therapeutics | 2001 |
Expression of sodium pump isoforms and other sodium or calcium ion transporters in the heart of hypertensive patients
H Jäger, G Wozniak, IH Akintürk, FW Hehrlein, G Scheiner-Bobis |
Biochimica et Biophysica Acta (BBA) - Biomembranes | 2001 |
THE DECOMPENSATED DETRUSOR IV: EXPERIMENTAL BLADDER OUTLET OBSTRUCTION AND ITS FUNCTIONAL CORRELATION TO THE EXPRESSION OF THE RYANODINE AND VOLTAGE OPERATED CALCIUM CHANNELS
R Stein, JC Hutcheson, C Gong, DA Canning, MC Carr, SA Zderic |
The Journal of Urology | 2001 |
Up-regulation of inositol 1,4,5 trisphosphate receptor expression in atrial tissue in patients with chronic atrial fibrillation
J Yamada, T Ohkusa, T Nao, T Ueyama, M Yano, S Kobayashi, K Hamano, K Esato, M Matsuzaki |
Journal of the American College of Cardiology | 2001 |
Calcium signaling mechanisms in dedifferentiated cardiac myocytes: comparison with neonatal andadult cardiomyocytes
BJ Poindexter, JR Smith, LM Buja, RJ Bick |
Cell Calcium | 2001 |
Ryanodine Receptors/Calcium Release channels in Heart Failure and Sudden Cardiac Death
AR Marks |
Journal of Molecular and Cellular Cardiology | 2001 |
Reperfusion Arrhythmias: New Insights into the Role of the Na+/Ca2+Exchanger
DR van Wagoner, M Bond |
Journal of Molecular and Cellular Cardiology | 2001 |
cADP-ribose/ryanodine channel/Ca 2+ -release signal transduction pathway in mesangial cells
AN Yusufi, J Cheng, MA Thompson, TP Dousa, GM Warner, HJ Walker, JP Grande |
American journal of physiology. Renal physiology | 2001 |
Sarcoplasmic Reticulum Ca 2+ ATPase (SERCA) 1a Structurally Substitutes for SERCA2a in the Cardiac Sarcoplasmic Reticulum and Increases Cardiac Ca 2+ Handling Capacity
MJ Lalli, J Yong, V Prasad, K Hashimoto, D Plank, GJ Babu, D Kirkpatrick, RA Walsh, M Sussman, A Yatani, E Marbán, M Periasamy |
Circulation research | 2001 |
β-Adrenergic Receptor Blockers Restore Cardiac Calcium Release Channel (Ryanodine Receptor) Structure and Function in Heart Failure
S Reiken, M Gaburjakova, J Gaburjakova, K He, A Prieto, E Becker, G Yi, J Wang, D Burkhoff, AR Marks |
Circulation | 2001 |
A Mechanistic Analysis of Reduced Mechanical Performance in Human Heart Failure
NR ALPERT, G HASENFUSS, BJ LEAVITT, FP ITTLEMAN, B PIESKE, LA MULIERI |
Japanese Heart Journal | 2000 |
Molecular aspects of arrhythmias associated with cardiomyopathies
GF Tomaselli, J Rose |
Current Opinion in Cardiology | 2000 |
Myocyte contractile dysfunction with hypertrophy and failure: Relevance to cardiac surgery
CA Walker, FA Crawford, FG Spinale |
The Journal of Thoracic and Cardiovascular Surgery | 2000 |
Left ventricular assist device-induced reverse ventricular remodeling
D Burkhoff, JW Holmes, J Madigan, A Barbone, MC Oz |
Progress in Cardiovascular Diseases | 2000 |
Cellular Events Linked to Cardiac Remodeling in Heart Failure: Targets for Pharmacologic Intervention:
MR Piano, SD Kim, C Jarvis |
The Journal of cardiovascular nursing | 2000 |
Abnormal intracellular Ca2+homeostasis and disease
L Missiaen, W Robberecht, LV Bosch, G Callewaert, JB Parys, F Wuytack, L Raeymaekers, B Nilius, J Eggermont, HD Smedt |
Cell Calcium | 2000 |
Abnormalities of Calcium Cycling in the Hypertrophied and Failing Heart
SR Houser, V Piacentino, J Weisser |
Journal of Molecular and Cellular Cardiology | 2000 |
Cardiac Intracellular Calcium Release Channels: Role in Heart Failure
AR Marks |
Circulation research | 2000 |
Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure
PM Heerdt, JW Holmes, B Cai, A Barbone, JD Madigan, S Reiken, DL Lee, MC Oz, AR Marks, D Burkhoff |
Circulation | 2000 |
Chronic α-Adrenergic Receptor Stimulation Modulates the Contractile Phenotype of Cardiac Myocytes In Vitro
N Satoh, TM Suter, R Liao, WS Colucci |
Circulation | 2000 |
Surgical Options for the Treatment of Heart Failure
RG Masters |
2000 | |
Molecular Approaches to Heart Failure Therapy
G Hasenfuss, E Marbán |
2000 | |
Myocardial region (right or left ventricle) and aetiology of heart failure can influence the inotropic effect of ouabain in failing human myocardium
R Padrini, M Panfili, G Magnolfi, D Piovan, D Casarotto, M Ferrari |
British Journal of Clinical Pharmacology | 1999 |
Expression and subcellular localization of the ryanodine receptor in rat pancreatic acinar cells
MF Leite, JA Dranoff, L Gao, MH Nathanson |
Biochemical Journal | 1999 |
Intracellular Calcium Release Channel Expression during Embryogenesis
N Rosemblit, MC Moschella, EO s̆, DE Gutstein, KO s̆, AR Marks |
Developmental Biology | 1999 |
Dantrolene sodium improves the force-frequency relationship and β-adrenergic responsiveness in failing human myocardium
A Meissner, JY Min, N Haake, S Hirt, R Simon |
European Journal of Heart Failure | 1999 |
Expression of inositol trisphosphate receptors
CW Taylor, AA Genazzani, SA Morris |
Cell Calcium | 1999 |
Molecular Mechanisms of Myocardial Remodeling
B Swynghedauw |
Physiological reviews | 1999 |
Reduced Subendocardial Ryanodine Receptors and Consequent Effects on Cardiac Function in Conscious Dogs With Left Ventricular Hypertrophy
L Hittinger, B Ghaleh, J Chen, JG Edwards, RK Kudej, M Iwase, SJ Kim, SF Vatner, DE Vatner |
Circulation research | 1999 |
Sarcoplasmic Reticulum Proteins in Heart Failure
SE Lehnart, W Schillinger, B Pieske, J Prestle, H Just, G Hasenfuss |
Annals of the New York Academy of Sciences | 1998 |
Sarcoplasmic reticulum in heart failure: central player or bystander?
RM Phillips, P Narayan, AM Gómez, K Dilly, LR Jones, WJ Lederer, RA Altschuld |
Cardiovascular Research | 1998 |
Alterations of calcium-regulatory proteins in heart failure
G Hasenfuss |
Cardiovascular Research | 1998 |
Cellular Distribution of Ca 2+ Pumps and Ca 2+ Release Channels in Rat Cardiac Hypertrophy Induced by Aortic Stenosis
M Anger, AM Lompré, O Vallot, F Marotte, L Rappaport, JL Samuel |
Circulation | 1998 |
Alterations of Excitation-Contraction Coupling in the Failing Human Heart
G Hasenfuss, H Just |
1998 | |
Calcium channel blockers in cardiac failure
N Mahon, WJ McKenna |
Progress in Cardiovascular Diseases | 1998 |
Differences in sarcoplasmic reticulum gene expression in myocardium from patients undergoing cardiac surgery. Quantification of steady-state levels of messenger RNA using the reverse transcription-polymerase chain reaction
T Ohkusa, T Noma, T Ueyama, Y Hisamatsu, M Yano, K Esato, A Nakazawa, M Matsuzaki |
Heart and Vessels | 1997 |
Intracellular calcium signalling in striated muscle cells
PK Lunde, OM Sejersted |
Scandinavian Journal of Clinical & Laboratory Investigation | 1997 |
Advances in Molecular and Cell Biology
KJ Clemetson |
Advances in Molecular and Cell Biology | 1997 |
The Two Intracellular Ca2+Release Channels, Ryanodine Receptor and Inositol 1,4,5-Trisphosphate Receptor, Play Different Roles during Fertilization in Ascidians
M Albrieux, C Sardet, M Villaz |
Developmental Biology | 1997 |
Identification and Functional Reconstitution of the Type 2 Inositol 1,4,5-Trisphosphate Receptor from Ventricular Cardiac Myocytes
PJ Perez, J Ramos-Franco, M Fill, GA Mignery |
The Journal of biological chemistry | 1997 |
Calcium handling proteins in the failing human heart
G Hasenfuss, M Meyer, W Schillinger, M Preuss, B Pieske, H Just |
Basic Research in Cardiology | 1997 |
Cardiac surgical implications of calcium dyshomeostasis in the heart
DR Meldrum, JC Cleveland, BC Sheridan, RT Rowland, A Banerjee, AH Harken |
The Annals of Thoracic Surgery | 1996 |
Expression and regulation of ryanodine receptor/calcium release channels
AR Marks |
Trends in Cardiovascular Medicine | 1996 |
Biochemical Mechanisms in Heart Function
EG Krause, R Vetter |
1996 | |
Molecular Physiology and Pharmacology of Cardiac Ion Channels and Transporters
M Morad, S Ebashi, W Trautwein, Y Kurachi |
1996 | |
Physiologic and emerging pathophysiologic role of cardiac calcium channels
PJ Gengo |
Heart Failure Reviews | 1996 |
Unaltered ryanodine receptor protein levels in ischemic cardiomvopathy
W Schillinger, M Meyer, G Kuwajima, K Mikoshiba, H Just, G Hasenfuss |
Molecular and Cellular Biochemistry | 1996 |
Calciumantagonisten
W Kübler, HA Tritthart |
1996 | |
Calreticulin
M Michalak, RE Milner, K Burns, M Opas |
Biochemical Journal | 1992 |
International Review of Cytology
RA Miller |
International Review of Cytology | 1991 |