期刊
ANNALS OF MEDICINE
卷 32, 期 8, 页码 572-578出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/07853890008998837
关键词
cardiac contractility; phospholamban; relaxation; sarcoplasmic reticulum
资金
- NCRR NIH HHS [P40 RR 12358] Funding Source: Medline
- NHLBI NIH HHS [HL26057, HL64018] Funding Source: Medline
Over the last three decades, our knowledge and understanding of the role of phospholamban and its modulation of sarcoplasmic reticulum (SR) function has advanced significantly. Phospholamban is a key regulator of cardiac contractility and modulates SR Ca2+ sequestration by inhibiting the SR Ca2+ -ATPase (SERCA) in its dephosphorylated state. Upon phosphorylation, which is mediated through beta -adrenergic stimulation, the inhibitory effect of phospholamban on the function of SERCA is relieved. This review summarizes recent advances that have been made towards understanding the modulation of SR Ca2+-sequestration by phospholamban through the generation and characterization of genetically altered animal models. It also discusses the role of phospholamban in human heart failure and recent attempts to restore SR function in experimentally induced and human heart failure, which may be translated into future therapeutic approaches in the treatment of this disease.
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