EC-coupling in normal and failing hearts.
Systolic heart failure may be due to too few cardiomyocytes, or to reduced contractile function of the heart cells. In the latter situation the myocardial function is impaired and this condition is called myocardial failure. The pathophysiological mechanism behind this cellular defect is not known, but Ca2+ handling is altered. Although the most important trigger of sarcoplasmatic reticulum (SR) Ca2+ release, the L-type Ca2+ current, seems to be unaltered, SR Ca2+ load is reduced in human heart failure. This could explain the reduced contractility observed in failing hearts. Three possible mechanisms have been suggested to explain the reduction in SR Ca2+ load. They are leak through the SR Ca2+ release channel (RyR), impaired SR Ca2+ ATPase (SERCA) function and increased Na+/Ca2+-exchanger (NCX) function. Leak through RyR is not consistently found. Increased NCX function is probably secondary to a change in Ca2+ handling, and thus not a primary mechanism, but blockade of the NCX might have therapeutic potential. Reduced SERCA function is probably a primary mechanism for the observed systolic dysfunction, and further insight is to be gained through studies in genetically modified models.
Birkeland
Jon Arne
JA
Institute for Experimental Medical Research, Ullevål University Hospital, University of Oslo, Oslo, Norway. j.a.birkeland@medisin.uio.no
Sejersted
Ole M
OM
Taraldsen
Tore
T
Sjaastad
Ivar
I
D000200:Action Potentials; D000818:Animals; D020013:Calcium Signaling; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D004594:Electrophysiology; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D012680:Sensitivity and Specificity; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology*
D019831:Sodium-Calcium Exchanger; D000252:Calcium-Transporting ATPases