Sodium- and calcium-dependent steps in the mechanism of neonatal rat cardiac myocyte killing by ionophores. II. The calcium-carrying ionophore, A23187.
Sodium- and calcium-dependent steps in the mechanism of neonatal rat cardiac myocyte killing by ionophores. II. The calcium-carrying ionophore, A23187.
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离子载体杀死新生大鼠心肌细胞机制中的钠和钙依赖性步骤。
DOI：
10.1016/0041-008x(92)90143-g
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发表时间：
1992
影响因子：
3.8
通讯作者：
Shier,WT
中科院分区：
文献类型：
--
作者：
DuBourdieu,DJ;Shier,WT
一些证据表明，细胞内Ca 2+升高的作用机制诱导的细胞杀伤的各种代理。心肌细胞在各种条件下，包括缺血和暴露于莫能菌素，都容易被杀死。为了描述心肌细胞易受Ca 2+依赖的细胞杀伤机制，我们研究了Ca 2+加二价阳离子离子载体A23187杀死心肌细胞的机制。已经获得了两个Ca 2+介导的损伤步骤，随后是Na+介导的步骤，导致细胞死亡，检测为膜透化到台盼蓝染料。第一个Ca 2+介导的步骤需要A23187的存在和低的细胞外Ca 2+浓度（1-100 μm），并被Mn 2+和Ni 2+离子抑制。第二个钙依赖性步骤需要细胞外钙浓度在大约生理范围内（>1 mm），不依赖于离子载体，也不受Mn 2+抑制。花生四烯酸的释放发生在两个钙离子介导的步骤，但主要是在第二步。第二个损伤步骤的特征在于可见的细胞肿胀和乳酸脱氢酶活性的释放。Na+依赖性步骤需要细胞外Na+等于或大于生理浓度的一半（即，≥75 mm）。离子半径小于Na+的Li+可以在Na+依赖步骤中部分取代Na+，而K+、Cs+、Rb+和NH 4+（离子半径较大）则不能。
Several lines of evidence indicate a role for elevated intracellular Ca2+in mechanisms of cell killing induced by a wide variety of agents. Cardiac myocytes are susceptible to killing under various conditions, including ischemia and exposure to monensin. In order to delineate the Ca2+-dependent cell killing mechanism(s) to which cardiac myocytes are susceptible, we have investigated the mechanism by which they are killed by Ca2+plus the divalent cation ionophore A23187. Evidence has been obtained for two Ca2+-mediated injury steps followed by a Na+-mediated step leading to cell death detected as membrane permeabilization to trypan blue dye. The first Ca2+-mediated step requires the presence of A23187 and low extracellular Ca2+concentrations (1–100 μm) and is inhibited by Mn2+and Ni2+ions. The second Ca2+-dependent step requires extracellular Ca2+concentrations in approximately the physiological range (>1 mm), is not dependent on ionophore, and is not inhibited by Mn2+. Arachidonic acid release occurs during both Ca2+-mediated steps, but mostly during the second step. The second injury step is characterized by visible cell swelling and release of lactate dehydrogenase enzyme activity. The Na+-dependent step requires extracellular Na+equal to or greater than half the physiological concentration (i.e., ≥75 mm). Li+, which has a smaller ionic radius than Na+, can partially substitute for it in the Na+-dependent step, whereas K+, Cs+, Rb+, and NH4+(which have larger ionic radii) cannot.
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影响因子：
7.3
作者：
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影响因子：
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影响因子：
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作者：
Kamitani,T;Little,MH;Ellis,EF
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