The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials.
The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials.
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DOI：
10.1007/s12013-016-0758-1
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发表时间：
2016-12
影响因子：
2.6
通讯作者：
Jacot, Jeffrey G.
中科院分区：
文献类型：
--
作者：
Boothe, Sean D.;Myers, Jackson D.;Pok, Seokwon;Sun, Junping;Xi, Yutao;Nieto, Raymond M.;Cheng, Jie;Jacot, Jeffrey G.
关键词：
心肌组织的硬度在出生时和新生儿发育过程中发生显著变化，同时心肌细胞的收缩和电成熟发生显著变化。我们小组以前的研究表明，当心肌细胞在硬度接近天然心脏组织的基质上培养时，心肌细胞产生最大的收缩力。然而，基板刚度对心肌细胞的电生理和离子电流的影响还没有得到充分的表征。在这项研究中，新生大鼠心室肌细胞培养的平面聚丙烯酰胺水凝胶的弹性模量范围从1至25 kPa的表面。采用全细胞膜片钳技术，记录动作电位和L型钙电流。在具有9 kPa弹性模量的水凝胶上培养的心肌细胞具有最长的动作电位时程，其弹性模量与天然心肌相似。此外，在弹性模量高于9 kPa的水凝胶上的心肌细胞中，最大钙通量时的电压显著降低，并且平均失活电压随着刚度的增加而降低。有趣的是，L型钙通道α亚基基因的表达和通道定位并不随刚度而改变。底物硬度显着影响动作电位长度和钙流量在培养的新生大鼠心肌细胞的方式，可能是无关的钙通道表达。这些结果可以解释在胚胎发育过程中观察到的细胞外基质的弹性模量的变化，在心肌梗死后的心脏缺血区域，并在扩张型心肌病引起的心肌细胞的功能差异。
The stiffness of myocardial tissue changes significantly at birth and during neonatal development, concurrent with significant changes in contractile and electrical maturation of cardiomyocytes. Previous studies by our group have shown that cardiomyocytes generate maximum contractile force when cultured on a substrate with a stiffness approximating native cardiac tissue. However, effects of substrate stiffness on the electrophysiology and ion currents in cardiomyocytes have not been fully characterized. In this study, neonatal rat ventricular myocytes were cultured on the surface of flat polyacrylamide hydrogels with elastic moduli ranging from 1 to 25 kPa. Using whole-cell patch clamping, action potentials and L-type calcium currents were recorded. Cardiomyocytes cultured on hydrogels with a 9 kPa elastic modulus, similar to that of native myocardium, had the longest action potential duration. Additionally, the voltage at maximum calcium flux significantly decreased in cardiomyocytes on hydrogels with an elastic modulus higher than 9 kPa, and the mean inactivation voltage decreased with increasing stiffness. Interestingly, the expression of the L-type calcium channel subunit α gene and channel localization did not change with stiffness. Substrate stiffness significantly affects action potential length and calcium flux in cultured neonatal rat cardiomyocytes in a manner that may be unrelated to calcium channel expression. These results may explain functional differences in cardiomyocytes resulting from changes in the elastic modulus of the extracellular matrix, as observed during embryonic development, in ischemic regions of the heart after myocardial infarction, and during dilated cardiomyopathy.
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影响因子：
2.4
作者：
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DOI：
10.1083/jcb.200405004
发表时间：
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期刊：
The Journal of cell biology
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