CONTROL OF THE NA-CA EXCHANGER IN ISOLATED HEART-CELLS .2. BEAT-DEPENDENT ACTIVATION IN NORMAL-CELLS BY INTRACELLULAR CALCIUM
CONTROL OF THE NA-CA EXCHANGER IN ISOLATED HEART-CELLS .2. BEAT-DEPENDENT ACTIVATION IN NORMAL-CELLS BY INTRACELLULAR CALCIUM
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DOI：
10.1161/01.res.69.6.1514
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发表时间：
1991-12-01
影响因子：
20.1
通讯作者：
GOKNUR, AB
中科院分区：
文献类型：
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作者：
HAWORTH, RA;GOKNUR, AB
用 Na-22 测量，以 4 Hz 电刺激悬浮的分离的成年大鼠心脏细胞，导致穿过肌膜的钠流入和流出速率增加四倍，而细胞钠总量没有变化。在这些条件下，刺激依赖性钠通量的大小平均为 17 nmol/min/mg 蛋白质。增加的流出率受到河豚毒素、维拉帕米或二氯苯甲酰胺的抑制，并且需要细胞外钙。 Bay K 8644 克服了河豚毒素的抑制作用。二氯苯甲酰胺仅轻微抑制静息细胞中 Na-22 流出的基础速率。刺激诱导的流出不受哇巴因的抑制，但在哇巴因存在的情况下，刺激使总钠的积累速率增加了 4 nmol/min/mg。这种增加被河豚毒素或维拉帕米抑制。添加 KCl 也可以诱导钙依赖性 Na-22 流入和流出速率的增加。这种现象可以被维拉帕米和二氯苯甲酰抑制，但不能被河鲀毒素抑制，并且可以被 EGTA 逆转，但只是在延迟后才逆转。我们得出以下结论。 1) 静止细胞中的 Na-Ca 交换器激活率不超过 10%。 2) 交换器被激发期间通过钙通道进入细胞的钙直接或间接激活。 3) 在该制剂中，激发引起的钠通量的主要部分是由Na-Ca交换器介导的，只有相对少量的钠通道直接参与。这些通道通过促进钙通道激活间接参与。 4）如果所有钙依赖性钠通量都是Na-Ca交换，那么每次通过交换器的钙通量将比通过钙通道的钙通量大大约七倍。然而，钙依赖性钠通量的未确定部分可能是通过活化的 Na-Ca 交换器进行的直接 Na-Na 交换。
Electrical stimulation of isolated adult rat heart cells in suspension at 4 Hz resulted in a fourfold increase in the rate of sodium influx and efflux across the sarcolemma, with no change in total cell sodium, as measured with Na-22. The magnitude of stimulation-dependent sodium fluxes under these conditions averaged 17 nmol/min/mg protein. The increased rate of efflux was inhibited by tetrodotoxin, verapamil, or dichlorobenzamil and required extracellular calcium. The inhibition by tetrodotoxin was overcome by Bay K 8644. The basal rate of Na-22 efflux in cells at rest was inhibited only slightly by dichlorobenzamil. The stimulation-induced efflux was not inhibited by ouabain, but in the presence of ouabain, stimulation increased the rate of accumulation of total sodium by 4 nmol/min/mg. This increase was inhibited by tetrodotoxin or verapamil. A calcium-dependent increase in rate of Na-22 influx and efflux could also be induced by KCl addition. This was inhibited by verapamil and dichlorobenzamil but not by tetrodotoxin and was reversed by EGTA, but only after a delay. We conclude the following. 1) The Na-Ca exchanger in cells at rest is no more than 10% activated. 2) The exchanger becomes activated directly or indirectly by calcium that enters the cell through calcium channels during excitation. 3) In this preparation the major part of excitation-induced sodium fluxes are mediated by the Na-Ca exchanger, with only a relatively small direct participation of sodium channels. These channels participate indirectly by promoting calcium channel activation. 4) If all the calcium-dependent sodium fluxes were Na-Ca exchange, then calcium flux through the exchanger per beat would be about sevenfold larger than that through the calcium channels. An undetermined part of the calcium-dependent sodium fluxes, however, could be a direct Na-Na exchange through the activated Na-Ca exchanger.