Effect of phorbol esters on contractile state and calcium flux in cultured chick heart cells.
Effect of phorbol esters on contractile state and calcium flux in cultured chick heart cells.
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佛波酯对培养鸡心脏细胞收缩状态和钙通量的影响。
DOI：
10.1152/ajpheart.1987.253.1.h205
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Smith,TW
中科院分区：
文献类型：
--
作者：
Leatherman,GF;Kim,D;Smith,TW
佛波酯是一种有效的肿瘤促进剂，由于其能够激活蛋白激酶C而被广泛应用于跨膜信号转导的研究。为了研究佛波酯(佛波酯)对心肌收缩的影响(以及间接的蛋白激酶C的作用)，我们在自发收缩培养的鸡心室肌细胞上观察了佛波酯(PMA)对心肌收缩状态、跨膜45Ca流量和胞浆游离钙浓度([Ca]i)的影响。PMA使细胞运动幅度呈浓度和时间依赖性降低[半数抑制浓度(IC50)=130 nM]，在1微米时作用最大(为对照的54+/-5%)。PMA(1微米)使45Ca摄取率降低16+/-4%(P<0.05)，使快速交换钙池的大小减少11+/-2%(P<0.05)，但不改变45Ca流出速率。在Fura-2负载的细胞中，PMA使[Ca]i从96+/-7 nM下降到72+/-5 nM(平均+/-SE；P<0.05)，其时间过程与收缩幅度的变化相似。PMA对细胞内Na含量无影响。佛波酯(1微米)是一种不能激活蛋白激酶C的佛波二酯，它对心肌收缩幅度、~(45)Ca流出和[Ca]i无明显影响。这些结果表明，PMA影响跨肌膜钙摄取，从而影响兴奋-收缩过程，提示蛋白激酶C可能调节心肌钙稳态和收缩状态。
Phorbol esters are potent tumor promoters that have been widely used in studies of transmembrane signaling because of their ability to activate protein kinase C. To study the effect of phorbol esters (and indirectly, the role of protein kinase C) on cardiac muscle contractility, we examined the effects of phorbol myristate acetate (PMA) on contractile state, transmembrane 45Ca fluxes, and cytosolic free Ca concentration ([Ca]i) using spontaneously contracting cultured chick ventricular cells. PMA produced a concentration- and time-dependent decrease in the amplitude of cell motion [half maximum inhibitory concentration (IC50) = 130 nM] with maximal effect (54 +/- 5% of control) observed at 1 microM. PMA (1 microM) reduced 45Ca uptake rate by 16 +/- 4% (P less than 0.05) and the size of the rapidly exchangeable Ca pool by 11 +/- 2% (P less than 0.05) but did not alter the 45Ca efflux rate. In fura-2-loaded cells, PMA produced a decrease in [Ca]i from 96 +/- 7 to 72 +/- 5 nM (mean +/- SE; P less than 0.05) with a time course similar to that of alteration in contractile amplitude. PMA had no effect on cellular Na content. Phorbol didecanoate (1 microM), a phorbol diester that does not activate protein kinase C, produced no significant changes in contractile amplitude, 45Ca fluxes, or [Ca]i. These results indicate that PMA influences transsarcolemmal Ca uptake, and thus the excitation-contraction process, and suggest that protein kinase C may modulate myocardial Ca homeostasis and contractile state.