Modulation of L-type Ca2+ channel activity by neuronal nitric oxide synthase and myofilament Ca2+ sensitivity in cardiac myocytes from hypertensive rat
Modulation of L-type Ca2+ channel activity by neuronal nitric oxide synthase and myofilament Ca2+ sensitivity in cardiac myocytes from hypertensive rat
复制标题
神经元一氧化氮合酶对高血压大鼠心肌细胞 L 型 Ca2 通道活性和肌丝 Ca2 敏感性的调节
DOI：
10.1016/j.ceca.2015.06.004
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发表时间：
2015-09-01
期刊：
影响因子：
4
通讯作者：
Zhang, Yin Hua
中科院分区：
文献类型：
--
作者：
Wang, Yue;Youm, Jae Bourn;Zhang, Yin Hua
神经元型一氧化氮合酶（nNOS）在病变心脏保护中起重要作用。最近，我们报道了nNOS与高血压大鼠心肌细胞肌丝Ca2+脱敏有关。迄今为止，肌丝Ca2+脱敏或nNOS对心肌细胞l型Ca2+通道活性（I-Ca）的影响尚不清楚。在这里，我们检测了nNOS对假手术和血管紧张素II （Ang II）诱导的高血压大鼠左心室（LV）肌细胞中I-Ca的调节。我们的研究结果显示，假手术和高血压之间的基础I-Ca没有差异（从-60到+40 mV， 0.1 Hz）。s -甲基- l-硫辛瓜氨酸（SMTC）是一种选择性的nNOS抑制剂，两组的I-Ca峰升高相似。然而，细胞内Ca2+ [Ca2+](i)与BAPTA的螯合作用增加了i - ca，并仅在高血压中消除了smtc增加的i - ca。用丁二酮单肟（BDM）（一种肌球蛋白atp酶抑制剂）对肌丝Ca2+脱敏，在两组中都降低了I-Ca，但在高血压中程度更大。在BDM存在的情况下，细胞内BAPTA或nNOS抑制使I-Ca恢复到基础水平，表明nNOS对Ca2+依赖性I-Ca失活和高血压的易感性更大。增加刺激频率（2、4和8 Hz）减弱假手术肌丝Ca2+敏感性，降低两组I-Ca峰值。然而，SMTC或BAPTA对两组高频率的I-Ca没有影响。这些结果表明，nNOS通过Ca2+依赖机制减弱I-Ca，并且在肌丝Ca2+脱敏的高血压患者中易感性更大。在高刺激频率下，nNOS或[Ca2+](i)不影响i - ca。结果用计算机模拟得到了概括。(C) 2015 Elsevier Ltd.版权所有。
Neuronal nitric oxide synthase (nNOS) is important in cardiac protection in diseased heart. Recently, we have reported that nNOS is associated with myofilament Ca2+ desensitization in cardiac myocytes from hypertensive rats. So far, the effect of myofilament Ca2+ desensitization or nNOS on L-type Ca2+ channel activity (I-Ca) in cardiac myocyte is unclear. Here, we examined nNOS regulation of I-Ca in left ventricular (LV) myocytes from sham and angiotensin II (Ang II)-induced hypertensive rats.Our results showed that basal I-Ca was not different between sham and hypertension (from -60 to +40 mV, 0.1 Hz). S-methyl-L-thiocitrulline (SMTC), a selective nNOS inhibitor, increased peak I-Ca similarly in both groups. However, chelation of intracellular Ca2+ [Ca2+](i) with BAPTA increased I-Ca and abolished SMTC-augmentation of I-Ca only in hypertension. Myofilament Ca2+ desensitization with butanedione monoxime (BDM), a myosin ATPase inhibitor, decreased I-Ca in both groups but to a greater extent in hypertension. Intracellular BAPTA or nNOS inhibition reinstated I-Ca in the presence of BDM to the basal level, suggesting Ca2+-dependent inactivation of I-Ca by nNOS and greater vulnerability in hypertension. Increasing stimulation frequencies (2, 4 and 8 Hz) attenuated myofilament Ca2+ sensitivity in sham and reduced peak I-Ca in both groups. Nevertheless, SMTC or BAPTA exerted no effect on I-Ca at high frequencies in either group.These results suggest that nNOS attenuates I-Ca via Ca2+-dependent mechanism and the vulnerability is greater in hypertension subject to myofilament Ca2+ desensitization. nNOS or [Ca2+](i) does not affect I-Ca at high stimulation frequencies. The results were recapitulated with computer simulation. (C) 2015 Elsevier Ltd. All rights reserved.