Neural remodeling may partly contribute to the abnormality of excitation-contraction coupling in heart failure.
Heart failure (HF) is a major and growing public health problem in the world. About 50% of deaths in HF occur suddenly due to malignant arrhythmia. Therefore, exploring the further mechanisms of chronic HF and finding new therapy targets are essential for the progression of HF treatment. Recently, some published papers suggested that myocardial neural remodeling and abnormal excitation-contraction (EC) coupling might partly contribute to the development of HF and sudden cardiac death. Even though a few studies have demonstrated that the sympathetic nerve system (SNS) may have significant impact on the functional states of myocardial EC coupling through the beta-adrenergic signaling pathway, so far, it still remains unknown that whether neural remodeling affects the EC coupling. Studies from Marks' group demonstrated that 70% of cardiac ryanodine receptors (RyR2), which located on the sarcoplasmic reculum (SR) controlling intracellular Ca(2+) release and muscle contraction in the heart, from failing hearts were abnormal and only 15% exhibited the most severe defects. In addition, Litwin et al. observed that temporal and spatial heterogeneities in local Ca(2+) release events in a rabbit model of HF after myocardial infarction. Because some studies have demonstrated that chronic SNS hyperactivity in HF led to protein kinase A (PKA) hyperphosphorylation of RyR2 in the heart, and the myocardial sympathetic nerve distribution become heterogeneous in the setting of HF. Thus, it is reasonable for us to propose the hypothesis that neural remodeling may partly account for the abnormality of EC coupling in HF.
Chen
Kang-Yin
KY
Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China. chenkangyin@hotmail.com
Li
Yong-Jian
YJ
Huang
Ti-Gang
TG
Li
Yu-Ming
YM
D002118:Calcium / Q000502:physiology; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D008959:Models, Neurological; D009200:Myocardial Contraction / Q000502:physiology*
D002118:Calcium