本文選題：低氧 + 晚鈉電流��； 參考：《武漢科技大學(xué)》2015年碩士論文

【摘要】：研究表明，低氧能增大心室肌細(xì)胞晚鈉電流（Late sodium current, INa.L），并進(jìn)一步引起反向鈉鈣交換電流（reverse Na+-Ca2+exchanger current, INCX）增強導(dǎo)致細(xì)胞內(nèi)鈣超載，但其機(jī)制尚未闡明。本文采用全細(xì)胞和單通道（貼附式）膜片鉗技術(shù)記錄心室肌細(xì)胞INa.L和及用全細(xì)胞模式記錄反向INCX，探討低氧條件下導(dǎo)致心室肌細(xì)胞INa.L增大的細(xì)胞內(nèi)信號轉(zhuǎn)導(dǎo)途徑及其與胞內(nèi)鈣超載的關(guān)系。結(jié)果表明，低氧可使INa.L密度從㧟0.31±0.02pA/pF增大到㧟0.66±0.03pA/pF（n=6，P0.01versus control），加入CaMⅡ特異性阻斷劑KN-93（1μM）后，增大的INa.L減小到㧟0.44±0.03pA/pF（n=6，P0.01versus hypoxia）。低氧還可使反向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密度減小到1.36±0.15pA/pF（n=7，P0.01versus hypoxia）。此外，當(dāng)?shù)脱跏笽Na.L密度從㧟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）抑制劑BisindolyImaleimideⅥ(BIM，1μM)，增大的INa.L被減小到㧟0.48±0.02pA/pF（n=6，P0.01versushypoxia）。當(dāng)?shù)脱跏笽NCX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可使其減小到1.33±0.21pA/pF（n=7，P0.01versus hypoxia）。Ca2+螯合劑BAPTA/AM（1mM，透膜型）可使低氧增大的INa.（L從㧟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）分別減少到㧟0.39±0.02pA/pF（n=6，，P0.01versus hypoxia）和1.12±0.27pA/pF（n=7，P0.01versus hypoxia）。單通道記錄模式中，低氧增大并延長INa.L的開放概率和開放時間,灌流液中加入KN-93（1μM）或BAPTA/AM（1mM）后，開放概率和開放時間可被明顯地減小和縮短。以上實驗結(jié)果表明：低氧可增大心室肌細(xì)INa.L和反向INCX，胞內(nèi)信號傳導(dǎo)系統(tǒng)中PKC和Ca2+/CaMKⅡ通路以及胞內(nèi)Ca2+都參與了低氧增大INa.L和反向INCX的過程。
[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 鹵0.02pA/pF to 0.66 鹵0.03pA / pFN / P0.01versus control. After adding CaM 鈪

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