Adult rat cardiomyocytes exhibit capacitative calcium entry
Adult rat cardiomyocytes exhibit capacitative calcium entry
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DOI：
10.1152/ajpheart.00162.2003
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发表时间：
2004-03-01
影响因子：
4.8
通讯作者：
Marchase, RB
中科院分区：
文献类型：
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作者：
Hunton, DL;Zou, LY;Marchase, RB
容量性钙内流（Capacitative Ca 2 + entry，CCE）是指内质网-肌浆网Ca 2+库耗竭时，Ca 2+通过激活的质膜通道内流的过程。我们利用两个钙敏感染料（一个监测细胞质游离钙2+和其他游离钙2+肌浆网内），以确定是否成年大鼠心室肌细胞表现出CCE。用肌质内质网Ca ~（2+）-ATP酶抑制剂处理不能有效地释放Ca ~（2+）。然而，当这些抑制剂与Ca 2+离子载体或血管紧张素II（一种产生肌醇1，4，5三磷酸的激动剂）偶联时，观察到储存的消耗。这种消耗伴随着显着的细胞外Ca 2+的CCE特性的流入。当咖啡因耗尽时，也观察到CCE。这种Ca 2+内流对CCE的四种抑制剂（葡萄糖胺、镧、钆和SKF-96365）敏感，但对L型通道或Na+/Ca 2+交换剂的抑制剂不敏感。在全细胞构型中，当移液器中含有Ca ~（2+）螯合剂或（1，4，5）-三磷酸肌醇时，或当用Ca ~（2+）-ATP酶抑制剂和离子载体耗尽Ca ~（2+）库时，在-90 mV下激活的内向电流约为0.7 pA/pF。电流在超极化电压下最大并向内整流。该通道对Ca ~（2+）和Ba ~（2+）有较强的渗透性，但对Mg ~（2+）和Mn ~（2+）的渗透性较差。总之，这些数据支持CCE在成年心肌细胞中的存在，这一发现可能与磷脂酶C生成激动剂的生理反应有关。
Capacitative Ca2+ entry (CCE) refers to the influx of Ca2+ through plasma membrane channels activated on depletion of endoplasmic-sarcoplasmic reticulum Ca2+ stores. We utilized two Ca2+-sensitive dyes (one monitoring cytoplasmic free Ca2+ and the other free Ca2+ within the sarcoplasmic reticulum) to determine whether adult rat ventricular myocytes exhibit CCE. Treatments with inhibitors of the sarcoplasmic endoplasmic reticulum Ca2+-ATPases were not efficient in releasing Ca2+ from stores. However, when these inhibitors were coupled with either Ca2+ ionophores or angiotensin II (an agonist generating inositol 1,4,5 trisphosphate), depletion of stores was observed. This depletion was accompanied by a significant influx of extracellular Ca2+ characteristic of CCE. CCE was also observed when stores were depleted with caffeine. This influx of Ca2+ was sensitive to four inhibitors of CCE (glucosamine, lanthanum, gadolinium, and SKF-96365) but not to inhibitors of L-type channels or the Na+/Ca2+ exchanger. In the whole cell configuration, an inward current of similar to0.7 pA/pF at -90 mV was activated when a Ca2+ chelator or inositol (1,4,5)-trisphosphate was included in the pipette or when Ca2+ stores were depleted with a Ca2+-ATPase inhibitor and ionophore. The current was maximal at hyperpolarizing voltages and inwardly rectified. The channel was relatively permeant to Ca2+ and Ba2+ but only poorly to Mg2+ or Mn2+. Taken together, these data support the existence of CCE in adult cardiomyocytes, a finding with likely implications to physiological responses to phospholipase C-generating agonists.