Carnosine is a novel peptide modulator of intracellular calcium and contractility in cardiac cells
Carnosine is a novel peptide modulator of intracellular calcium and contractility in cardiac cells
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DOI：
10.1152/ajpheart.1997.272.1.h462
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发表时间：
1997-01-01
影响因子：
4.8
通讯作者：
Nelson, TE
中科院分区：
文献类型：
--
作者：
Zaloga, GP;Roberts, PR;Nelson, TE
心肌收缩衰竭是缺血性心脏病和败血症等全身炎症状态患者发病和死亡的常见原因。越来越多的证据表明收缩衰竭与肌浆钙水平失调有关。在寻找收缩功能障碍的生化原因时，我们发现二肽肌肽可以改善心肌收缩力，并测试了肌肽在细胞内钙调节中发挥作用的可能性。肌肽以剂量依赖性方式（1-10 mM）增加离体灌注大鼠心脏的收缩性，并且还增加离体心肌细胞中游离细胞内钙的水平。肌肽通过从带皮心肌纤维中的兰尼碱受体钙释放通道释放钙来增加心肌细胞张力，并增加脂质双层中分离的兰尼碱受体钙释放通道的开放状态概率和停留时间。此外，我们报告肌肽使收缩蛋白对钙敏感。这些结果表明肌肽作为细胞内钙和心脏组织收缩性调节剂的新作用。
Myocardial contractile failure is a common cause of morbidity and mortality in patients with ischemic heart disease and systemic inflammatory states such as sepsis. Accumulating evidence indicates that contractile failure is associated with dysregulation of myoplasmic calcium levels. In a search for biochemical causes for contractile dysfunction, we found that the dipeptide carnosine improves cardiac contractility and tested the possibility that carnosine plays a role in the regulation of intracellular calcium. Carnosine increased contractility in a dose-dependent manner (1-10 mM) in isolated perfused rat hearts, and it also increased free intracellular calcium levels in isolated myocytes. Carnosine increased myocyte tension via calcium release from the ryanodine receptor calcium release channel in skinned myocardial fibers and increased open-state probability and dwell time of the isolated ryanodine receptor calcium release channel in Lipid bilayers. In addition, we report that carnosine sensitizes the contractile proteins to calcium. These results suggest a novel role for carnosine as a modulator of intracellular calcium and contractility in cardiac tissue.