低氧诱导增大的心室肌晚钠电流导致细胞内钙超载的机制研究
发布时间：2018-04-28 15:01
本文选题：低氧 + 晚钠电流 ； 参考：《武汉科技大学》2015年硕士论文
【摘要】：研究表明，低氧能增大心室肌细胞晚钠电流（Late sodium current, INa.L），并进一步引起反向钠钙交换电流（reverse Na+-Ca2+exchanger current, INCX）增强导致细胞内钙超载，但其机制尚未阐明。本文采用全细胞和单通道（贴附式）膜片钳技术记录心室肌细胞INa.L和及用全细胞模式记录反向INCX，探讨低氧条件下导致心室肌细胞INa.L增大的细胞内信号转导途径及其与胞内钙超载的关系。结果表明，低氧可使INa.L密度从㧟0.31±0.02pA/pF增大到㧟0.66±0.03pA/pF（n=6，P0.01versus control），加入CaMⅡ特异性阻断剂KN-93（1μM）后，增大的INa.L减小到㧟0.44±0.03pA/pF（n=6，P0.01versus hypoxia）。低氧还可使反向INCX密度由1.02±0.06pA/pF增大到1.91±0.20pA/pF（n=7，P0.01versus control），加入1μM/L KN-93后INCX密度减小到1.36±0.15pA/pF（n=7，P0.01versus hypoxia）。此外，当低氧使INa.L密度从㧟0.30±0.03pA/pF增大到㧟0.60±0.03pA/pF（n=6，P0.01versus control）之后，加入蛋白激酶C（PKC）抑制剂BisindolyImaleimideⅥ(BIM，1μM)，增大的INa.L被减小到㧟0.48±0.02pA/pF（n=6，P0.01versushypoxia）。当低氧使INCX密度由0.91±0.10pA/pF增大到1.71±0.27pA/pF（n=7，P0.01versus control）之后，1μM/L BIM可使其减小到1.33±0.21pA/pF（n=7，P0.01versus hypoxia）。Ca2+螯合剂BAPTA/AM（1mM，透膜型）可使低氧增大的INa.（L从㧟0.26±0.04pA/pF增大到㧟0.63±0.05pA/pF，n=6，P0.01versus control）和反向INC（X由0.86±0.09pA/pF增大到1.68±0.35pA/pF，n=7，P0.01versus control）分别减少到㧟0.39±0.02pA/pF（n=6，，P0.01versus hypoxia）和1.12±0.27pA/pF（n=7，P0.01versus hypoxia）。单通道记录模式中，低氧增大并延长INa.L的开放概率和开放时间,灌流液中加入KN-93（1μM）或BAPTA/AM（1mM）后，开放概率和开放时间可被明显地减小和缩短。以上实验结果表明：低氧可增大心室肌细INa.L和反向INCX，胞内信号传导系统中PKC和Ca2+/CaMKⅡ通路以及胞内Ca2+都参与了低氧增大INa.L和反向INCX的过程。
[Abstract]:It has been shown that hypoxia can increase late sodium current (late sodium current), INa.Ln and reverse Na Ca 2 2 exchanger current, INCX) increase in ventricular myocytes, but its mechanism has not been elucidated. In this paper, whole-cell and single-channel patch-clamp techniques were used to record INa.L in ventricular myocytes and reverse INCXs were recorded in whole-cell mode to investigate the intracellular signal transduction pathways leading to the increase of INa.L in ventricular myocytes under hypoxic conditions. The relationship between calcium overload and intracellular calcium overload. The results showed that hypoxia could increase the density of INa.L from 0.31 卤0.02pA/pF to 0.66 卤0.03pA / pFN / P0.01versus control. After adding CaM 鈪
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