L-Arginine currents in rat cardiac ventricular myocytes.
L-Arginine currents in rat cardiac ventricular myocytes.
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大鼠心室肌细胞中的 L-精氨酸电流。
DOI：
10.1113/jphysiol.2006.125054
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Peluffo,RDaniel
中科院分区：
文献类型：
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作者：
Peluffo,RDaniel
l-精氨酸（l-Arg）是一种碱性氨基酸，在一氧化氮、肌酸、胍丁胺、多胺、脯氨酸和谷氨酸的生物合成中起核心作用。大多数组织，包括心肌，必须从循环中输入l-Arg，以确保这种氨基酸的细胞内水平足够。本研究报告了全细胞电压钳位大鼠心室肌细胞中novell-Arg激活的内向电流。离子取代实验将细胞外l-Arg鉴定为负责这些电流的携带电荷的阳离子物质，因此，其代表l-Arg输入心肌细胞。这一结果通过在细胞外应用l-Arg时肌细胞一氧化氮产生的增加而得到独立证实。精氨酸分子的内向运动是被动的，不依赖于Na ~（2+）、K ~（2+）、Ca ~（2+）和Mg ~（2+）。该过程显示出饱和和膜电位（Vm）依赖性动力学，对于l-Arg的aK 0.5从5 mmat超极化Vm增加到20 mmat +40 mV。l-赖氨酸和l-鸟氨酸而不是l-Arg产生的电流具有与活化的l-Arg相似的特征，表明转运过程对阳离子l-氨基酸是立体特异性的。在与0.2 mmN-乙基马来酰亚胺短暂孵育后，l-Arg电流被完全阻断。这些特征表明，γ 2+转运蛋白家族的低亲和力、高容量CAT-2A成员的活性负责急性分离的心肌细胞中的l-Arg电流。无论机制如何，我们假设心脏中的低亲和力精氨酸转运过程，通过确保持续NO产生的底物可用性，可能在已知使精氨酸血浆水平增加数倍的分解代谢状态期间发挥心脏保护作用。
l‐Arginine (l‐Arg) is a basic amino acid that plays a central role in the biosynthesis of nitric oxide, creatine, agmantine, polyamines, proline and glutamate. Most tissues, including myocardium, must importl‐Arg from the circulation to ensure adequate intracellular levels of this amino acid. This study reports novell‐Arg‐activated inward currents in whole‐cell voltage‐clamped rat ventricular cardiomyocytes. Ion‐substitution experiments identified extracellularl‐Arg as the charge‐carrying cationic species responsible for these currents, which, thus, representl‐Arg import into cardiac myocytes. This result was independently confirmed by an increase in myocyte nitric oxide production upon extracellular application ofl‐Arg. The inward movement of Arg molecules was found to be passive and independent of Na2+, K2+, Ca2+and Mg2+. The process displayed saturation and membrane potential (Vm)‐dependent kinetics, with aK0.5forl‐Arg that increased from 5 mmat hyperpolarizingVmto 20 mmat +40 mV.l‐Lysine andl‐ornithine but notd‐Arg produced currents with characteristics similar to that activated byl‐Arg indicating that the transport process is stereospecific for cationicl‐amino acids.l‐Arg current was fully blocked after brief incubation with 0.2 mmN‐ethylmaleimide. These features suggest that the activity of the low‐affinity, high‐capacity CAT‐2A member of the y2+family of transporters is responsible forl‐Arg currents in acutely isolated cardiomyocytes. Regardless of the mechanism, we hypothesize that a low‐affinity arginine transport process in heart, by ensuring substrate availability for sustained NO production, might play a cardio‐protective role during catabolic states known to increase Arg plasma levels severalfold.