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首页> 外文期刊>Cellular Physiology and Biochemistry >ASIC-like Currents in Freshly Isolated Cerebral Artery Smooth Muscle Cells are Inhibited by Endogenous Oxidase Activity
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ASIC-like Currents in Freshly Isolated Cerebral Artery Smooth Muscle Cells are Inhibited by Endogenous Oxidase Activity

机译：内源性氧化酶活性抑制新鲜分离的脑动脉平滑肌细胞中的ASIC类电流。

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Background/Aims The aim of this study was to determine if VSMC ASIC-like currents are regulated by oxidative state. Methods We used whole-cell patch clamp of isolated mouse cerebral VSMCs to determine if 1) reducing agents, such as DTT and GSH, and 2) inhibition of endogenous oxidase activity from NADPH and Xanthine oxidases potentiate active currents and activate electrically silent currents. Results Pretreatment with 2 mM DTT or GSH, increased the mean peak amplitude of ASIC-like currents evoked by pH 6.0 from 0.4 ± 0.1 to 14.9 ± 3.6 pA/pF, and from 0.9 ± 0.3 to 11.3 ± 2.4 pA/pF, respectively. Pretreatment with apocynin, a NADPH oxidase inhibitor, mimics the effect of the reducing agents, with the mean peak current amplitude increased from 0.9 ± 0.5 to 7.0 ± 2.6 pA/pF and from 0.5 ± 0.2 to 26.4 ± 6.8 pA/pF by 50 and 200 µM apocynin, respectively. Pretreatment with allopurinol, a xanthine oxidase inhibitor, also potentiates the VSMC ASIC-like activity. Conclusion These findings suggest that VSMC ASIC-like channels are regulated by oxidative state and may be inhibited by basal endogenous oxidative sources such as NADPH and xanthine oxidase.
机译：背景/目的本研究的目的是确定类VSMC ASIC电流是否受氧化状态调节。方法我们使用分离的小鼠脑VSMC的全细胞膜片钳来确定1）还原剂，例如DTT和GSH，以及2）抑制NADPH和黄嘌呤氧化酶对内源性氧化酶活性的增效作用，并激活无声电流。结果用2 mM DTT或GSH预处理，pH 6.0引起的ASIC样电流的平均峰值幅度分别从0.4±0.1增至14.9±3.6 pA / pF和从0.9±0.3增至11.3±2.4 pA / pF。用NADPH氧化酶抑制剂Apocynin进行预处理可模仿还原剂的作用，平均峰值电流幅度从0.9±0.5增加到7.0±2.6 pA / pF，从0.5±0.2增加到26.4±6.8 pA / pF分别为50和分别为200 µM载脂蛋白。用黄嘌呤氧化酶抑制剂别嘌呤醇进行预处理也可以增强VSMC ASIC样活性。结论这些发现表明，VSMC ASIC样通道受氧化状态调节，并可能被基础内源性氧化源（如NADPH和黄嘌呤氧化酶）抑制。

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