[The mechanism of contractile dysfunction in heart failure, focussing on SERCA2a function].
Cytosolic Ca(2+) is a key regulator of excitation-contraction coupling in myocardium. Myocardial contractile dysfunction in heart failure is characterized by a decrease in contraction and prolonged relaxation. These alterations are mainly due to changes in 1) intracellular Ca(2+) transients (CaT), 2) Ca(2+) sensitivity of the contractile elements, and/or 3) contractile proteins. It is useful to investigate the relationship between CaT and contraction for understanding of the mechanism of contractile dysfunction in heart failure. There are many reports regarding the alterations in CaT, Ca(2+) sensitivity, and contractile proteins in heart failure. Changes in the activity of the sarcoplasmic Ca(2+) pump protein, SERCA2a, may be involved in the altered contractility in heart failure. We generated cardiac-restricted overexpression of SERCA2a transgenic mice (TG) and non-transgenic littermates (NTG). To investigate the role of SERCA2a activity for ischemic heart, we used acidosis as a model of acute contractile dysfunction. During acidosis and recovery from acidosis, the peaks of CaT and tension in TG were significantly larger than those in NTG. These results suggest that an increase in the activity of SERCA2a could be beneficial to preserve contractility during acidosis and recovery. Thus, a disturbance of the intracellular Ca(2+) homeostasis is one of the key factors for the contractile dysfunction in heart failure.
Kusakari
Yoichiro
Y
Department of Physiology (II), The Jikei University School of Medicine, Tokyo, Japan. kusakari@jikei.ac.jp
Hirano
Shuta
S
Hongo
Kenichi
K
Nakayama
Hiroyuki
H
Otsu
Kinya
K
Kurihara
Satoshi
S
D000138:Acidosis / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000502:physiology*; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium