Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure.
Cardiac hypertrophy and heart failure caused by high blood pressure were studied in single myocytes taken from hypertensive rats (Dahl SS/Jr) and SH-HF rats in heart failure. Confocal microscopy and patch-clamp methods were used to examine excitation-contraction (EC) coupling, and the relation between the plasma membrane calcium current (ICa) and evoked calcium release from the sarcoplasmic reticulum (SR), which was visualized as "calcium sparks." The ability of ICa to trigger calcium release from the SR in both hypertrophied and failing hearts was reduced. Because ICa density and SR calcium-release channels were normal, the defect appears to reside in a change in the relation between SR calcium-release channels and sarcolemmal calcium channels. beta-Adrenergic stimulation largely overcame the defect in hypertrophic but not failing heart cells. Thus, the same defect in EC coupling that develops during hypertrophy may contribute to heart failure when compensatory mechanisms fail.
Gómez
A M
AM
Department of Physiology and the Medical Biotechnology Center, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA. Universit.
Valdivia
H H
HH
Cheng
H
H
Lederer
M R
MR
Santana
L F
LF
Cannell
M B
MB
McCune
S A
SA
Altschuld
R A
RA
Lederer
W J
WJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D002462:Cell Membrane / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006973:Hypertension / Q000150:complications; D007545:Isoproterenol / Q000494:pharmacology; D018613:Microscopy, Confocal; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D009543:Nifedipine; D007545:Isoproterenol; D002118:Calcium