Molecular regulation of cardiac myocyte adaptations to chronic hypoxia.
Molecular regulation of cardiac myocyte adaptations to chronic hypoxia.
复制标题
DOI：
10.1016/0022-2828(92)93388-z
复制
发表时间：
1992-07
影响因子：
5
通讯作者：
Keith A. Webster;N. Bishopric;N. Bishopric
中科院分区：
文献类型：
--
作者：
Keith A. Webster;N. Bishopric;N. Bishopric
在心肌缺氧模型系统中研究慢性缺氧对离体新生大鼠心肌细胞的影响。将自发跳动的心肌细胞在氧压为 4 至 8 mmHg 的环境室内培养长达一周。为了模拟慢性流量减少的情况，经常补充新鲜的低氧培养基，以消除或最小化细胞外代谢物积累、pH 变化或能量消耗的影响。在这些条件下，与有氧培养相比，收缩逐渐受损且不规则，并且搏动频率在 3 天内下降至对照的 50% 左右。收缩力降低与细胞内基础 cAMP 水平逐渐降低同时发生。这两种效应都可以通过引入异丙肾上腺素来逆转。使用荧光钙螯合剂 Indo-1 进行钙通量可视化表明，较慢的收缩与肌肉松弛期间钙流出速率的显着降低相关。缺氧细胞中cAMP依赖性基因表达的变化是明显的，并且长期施用cAMP升高药物对缺氧下的细胞具有特异性毒性。我们认为cAMP可能调节心肌细胞对慢性缺氧的一些短期和长期适应。
The effects of chronic hypoxia on isolated neonatal rat cardiac myocytes were investigated in a model system of myocardial hypoxia. Spontaneously beating myocardiocytes were cultured for up to one week inside an environmental chamber at an oxygen tension of between 4 and 8 mmHg. In order to simulate a chronic reduced flow condition fresh hypoxic culture medium was replenished frequently to eliminate or minimize contributions of extracellular metabolite build-up, pH changes, or energy depletion. Under these conditions contractions became progressively impaired and irregular compared with aerobic cultures and beating frequency decreased to about 50% of control over 3 days. Reduced contractility was paralleled by a progressive decrease in the basal intracellular level of cAMP. Both of these effects could be reversed by introducing isoproterenol. Visualization of calcium fluxes using the fluorescent calcium chelator Indo-1 demonstrated that the slower contractions were associated with a pronounced decrease in the rate of calcium efflux during muscle relaxation. Changes in the expression of cAMP dependent genes was apparent in the hypoxic cells and the chronic administration of cAMP elevating drugs was toxic specifically to cells under hypoxia. We propose that cAMP may regulate some short and long-term adaptations of cardiac myocytes to chronic hypoxia.