Expression of calcium channels in adult cardiac myocytes is regulated by calcium
Expression of calcium channels in adult cardiac myocytes is regulated by calcium
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DOI：
10.1006/jmcc.1997.0406
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发表时间：
1997-07-01
影响因子：
5
通讯作者：
Marsh, JD
中科院分区：
文献类型：
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作者：
Davidoff, AJ;Maki, TM;Marsh, JD
细胞内Ca2+ ([Ca2+](i))除了在心脏兴奋-收缩偶联中发挥重要作用外，还可以调节基因表达。虽然调节Ca2+通道表达的机制尚未完全确定，但存在一些Ca2+依赖性调节的证据。利用成人心室肌细胞培养系统，我们确定了Ca2+对：(1)l型Ca2+通道α(1)亚基（DHP受体）mRNA丰度的影响；(2) DHP受体的数量；(3)全细胞Ca2+电流（I-Ca）。将大鼠心室肌细胞在含正常（1.8 mM）或高（4.8 mM） Ca2+的无血清培养基中培养1-3天。通过fura-2测定，肌细胞暴露于高Ca2+快速升高[Ca2+](i)。Northern blot分析显示，在高Ca2+环境中培养的细胞产生的DHP受体mRNA水平增加了1.5倍。通过配体结合确定的DHP受体的丰度在高Ca2+ 3天后的肌细胞中增加了两倍。此外，在高Ca2+ (-17.8 +/- 1.5 pA/pF, n=26)条件下培养3天的肌细胞的I-Ca峰值高于对照细胞（-11.0 +/- 1.0 pA/pF, n= 23）。在所有组中，Bay K8644引起的电压依赖性激活和失活、电流衰减率以及I-Ca的百分比增加是相似的。因此，较大的I-Ca可能代表更多数量的功能通道，而动力学不变。我们的数据支持这样的结论，即[Ca2+](i)的短暂变化可以调节DHP受体mRNA和蛋白质丰度，从而在成人心室肌细胞中产生相应的功能Ca2+通道变化。(C) 1997学术出版社有限公司
In addition to playing a significant role in cardiac excitation-contraction coupling, intracellular Ca2+ ([Ca2+](i)) can regulate gene expression. While the mechanisms regulating expression of Ca2+ channels are not entirely defined, some evidence exists for Ca2+-dependent regulation. Using an adult ventricular myocyte culture system, we determined the effects of Ca2+ on: (1) abundance of mRNA for L-type Ca2+ channel alpha(1) subunit (DHP receptor); (2) amount of DHP receptors; and (3) whole-cell Ca2+ current (I-Ca). Rat ventricular myocytes were cultured for 1-3 days in serum-free medium containing either normal (1.8 mM) or high (4.8 mM) Ca2+. Exposing myocytes to high Ca2+ rapidly elevated [Ca2+](i) as determined by fura-2. Northern blot analysis revealed that culturing cells in high Ca2+ produced similar to 1.5-fold increase in mRNA levels for the DHP receptor. The abundance of DHP receptors, determined by ligand binding, was two-fold greater in myocytes after 3 days in high Ca2+. Moreover, peak I-Ca, was larger in myocytes cultured for 3 days in high Ca2+ (-17.8 +/- 1.5 pA/pF, n=26) than in control cells (-11.0 +/- 1.0 pA/pF, n = 23). Voltage-dependent activation and inactivation, rates of current decay, as well as percent increases in I-Ca elicited by Bay K8644 were similar in all groups. Therefore, larger I-Ca, is likely to represent a greater number of functional channels with unchanged kinetics. Our data support the conclusion that transient changes in [Ca2+](i) can modulate DHP receptor mRNA and protein abundance, producing a corresponding change in functional Ca2+ channels in adult ventricular myocytes. (C) 1997 Academic Press Limited.