体外长期氧化负荷对豚鼠心室肌细胞电压依赖性钾电流的影响.doc
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体外长期氧化负荷对豚鼠心室肌细胞电压依赖性钾电流的影响,本文共7页 3913字摘要目的：研究豚鼠心室肌细胞在长期氧化负荷所致的细胞凋亡过程中延迟整流钾电流(ik)和内向整流钾电流(ik1)的改变。方法：采用50 μmol/l h2o2 诱导（24 h）培养的新生大鼠心肌细胞凋亡，并采用此剂量体外处理分离的成年豚鼠心室肌细...
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体外长期氧化负荷对豚鼠心室肌细胞电压依赖性钾电流的影响
本文共7页 3913字
摘要 目的：研究豚鼠心室肌细胞在长期氧化负荷所致的细胞凋亡过程中延迟整流钾电流(Ik)和内向整流钾电流(Ik1)的改变。方法：采用50 μmol/L H2O2 诱导（24 h）培养的新生大鼠心肌细胞凋亡，并采用此剂量体外处理分离的成年豚鼠心室肌细胞24小时。以TUNEL法评价细胞凋亡，膜片钳技术记录电压依赖性钾电流。结果：50 μmol/L H2O2 (24 h)能够明显诱导培养新生大鼠心肌细胞凋亡，此剂量处理分离的豚鼠心肌细胞24小时后，电压依赖性钾电流(Ik, Ik1)密度下调。+40 mV 测定电压下，对照组Ik电流密度为5.73±1.84pA/pF，50 μmol/L H2O2 组Ik电流密度为2.52±0.57pA/pF(n=8, P<0.01)； -120 mV和-40 mV测定电压下，对照组Ik1电流密度为-59.7±11.9 pA/pF和5.73±1.84 pA/pF，50 μmol/L H2O2 组Ik1电流密度为-13.9±2.7 pA/pF(n=8, P<0.01)和2.52±0.57 pA/pF(n=8, P<0.05)，50 μmol/L H2O2处理24小时减弱 Ik1 的内向整流特性。结论：豚鼠心室肌细胞在50 μmol/L H2O2处理24小时所致的细胞凋亡过程中，Ik, Ik1的电流密度均下降，而且Ik1的内向整流特性减弱。
关键词：过氧化氢，钾，凋亡，心肌细胞
ABSTRACT AIM: To determine the changes of delayed rectifier K+ currents(Ik) and inward rectifier K+ currents(Ik1) in the ventricular myocytes of guinea pigs during the gradual apoptotic process by the chronic oxidant stress treatment. METHODS: 50 μmol/L H2O2 (24 h) was examined for inducing apoptosis in the cardiomyocytes culture of neonatal rats and was used to treat the isolated ventricular myocytes of adult guinea pigs in vitro for 24 h. Apoptosis was evaluated by using TUNEL methods and voltage-dependent K+ currents were recorded by using patch-clamp techniques. RESULTS: 50 μmol/L H2O2 (24 h) induced cell apoptosis significantly in the cardiomyocytes culture of neonatal rats. This concentration was used to treat the isolated ventricular myocytes of adult guinea pigs in vitro for 24 h and the voltage-dependent K+ currents densities (Ik, Ik1) were down-regulated. The densities of the delayed rectifier K+ currents(Ik) in 50 μmol/L H2O2 group were 2.52±0.57 pA/pF vs 5.73±1.84 pA/pF in the control group at +50 mV(n=8, P<0.01); The densities of the inward rectifier K+ currents(Ik1) in 50 μmol/L H2O2 group were -13.9±2.70 pA/pF,
2.52±0.57 pA/pF vs -59.7±11.9 pA/pF, 5.73±1.84 pA/pF in the control group at -120 mV (n=8, P<0.01) and –40 mV(n=8, P<0.05), respectively. The extent of inward rectifier property of Ik1 was weakened by 50 μmol/L H2O2 treatment. CONCLUSION: The densities of Ik, Ik1 in the cardiomyocytes of guinea pigs were down-regulated and the inward rectifier property of Ik1 was weakened during the gradual apoptotic process by 50 μmol/L H2O2 treatment for 24h.
KEY WORDS hydrogen peroxide; potassium; apoptosis; cardiac
myocytes
参考文献:
1. Hughes FM Jr, Bortner CD, Purdy GD, Cidlowski JA. Intracellular K+ suppresses the activation of apoptosis in lymphocytes. J Biol Chem 1997; 272: 30567-76.
2. Yu SP, Yeh CH, Sensi SL, Gwag BJ, Canzoniero LM, Farhangrazi ZS et al. Mediation of neuronal apoptosis by enhancement of outward potassium current. Science 1997; 278: 114-7.
3. Yu SP, Yeh CH, Gottron F, Wang X, Grabb MC, Choi DW. Role of the outward delayed rectifier K+ current in ceramide-induced caspase activation and apoptosis in cultured cortical neurons. J Neuronchem 1999b; 73: 933-41.
4. Hubert h. Nietsch, Michael W. Roe, Jerome F. Fiekers, Ann L. Moore, and Steven D. Lidofsky. Activation of potassium and chloride channels by tumor necrosis factor α. Role in liver cell death. J Biol Chem 2000; 275: 20556-61.
5. Yu SP, Farhangrazi ZS, Ying HS, Yeh CH, Choi DW. Enhancement of outward potassium current may participate in beta-amyloid peptide-induced cortical neuronal death. Neurobiol Dis 1998; 5: 81-8.
本文共7页 3913字
摘要 目的：研究豚鼠心室肌细胞在长期氧化负荷所致的细胞凋亡过程中延迟整流钾电流(Ik)和内向整流钾电流(Ik1)的改变。方法：采用50 μmol/L H2O2 诱导（24 h）培养的新生大鼠心肌细胞凋亡，并采用此剂量体外处理分离的成年豚鼠心室肌细胞24小时。以TUNEL法评价细胞凋亡，膜片钳技术记录电压依赖性钾电流。结果：50 μmol/L H2O2 (24 h)能够明显诱导培养新生大鼠心肌细胞凋亡，此剂量处理分离的豚鼠心肌细胞24小时后，电压依赖性钾电流(Ik, Ik1)密度下调。+40 mV 测定电压下，对照组Ik电流密度为5.73±1.84pA/pF，50 μmol/L H2O2 组Ik电流密度为2.52±0.57pA/pF(n=8, P<0.01)； -120 mV和-40 mV测定电压下，对照组Ik1电流密度为-59.7±11.9 pA/pF和5.73±1.84 pA/pF，50 μmol/L H2O2 组Ik1电流密度为-13.9±2.7 pA/pF(n=8, P<0.01)和2.52±0.57 pA/pF(n=8, P<0.05)，50 μmol/L H2O2处理24小时减弱 Ik1 的内向整流特性。结论：豚鼠心室肌细胞在50 μmol/L H2O2处理24小时所致的细胞凋亡过程中，Ik, Ik1的电流密度均下降，而且Ik1的内向整流特性减弱。
关键词：过氧化氢，钾，凋亡，心肌细胞
ABSTRACT AIM: To determine the changes of delayed rectifier K+ currents(Ik) and inward rectifier K+ currents(Ik1) in the ventricular myocytes of guinea pigs during the gradual apoptotic process by the chronic oxidant stress treatment. METHODS: 50 μmol/L H2O2 (24 h) was examined for inducing apoptosis in the cardiomyocytes culture of neonatal rats and was used to treat the isolated ventricular myocytes of adult guinea pigs in vitro for 24 h. Apoptosis was evaluated by using TUNEL methods and voltage-dependent K+ currents were recorded by using patch-clamp techniques. RESULTS: 50 μmol/L H2O2 (24 h) induced cell apoptosis significantly in the cardiomyocytes culture of neonatal rats. This concentration was used to treat the isolated ventricular myocytes of adult guinea pigs in vitro for 24 h and the voltage-dependent K+ currents densities (Ik, Ik1) were down-regulated. The densities of the delayed rectifier K+ currents(Ik) in 50 μmol/L H2O2 group were 2.52±0.57 pA/pF vs 5.73±1.84 pA/pF in the control group at +50 mV(n=8, P<0.01); The densities of the inward rectifier K+ currents(Ik1) in 50 μmol/L H2O2 group were -13.9±2.70 pA/pF,
2.52±0.57 pA/pF vs -59.7±11.9 pA/pF, 5.73±1.84 pA/pF in the control group at -120 mV (n=8, P<0.01) and –40 mV(n=8, P<0.05), respectively. The extent of inward rectifier property of Ik1 was weakened by 50 μmol/L H2O2 treatment. CONCLUSION: The densities of Ik, Ik1 in the cardiomyocytes of guinea pigs were down-regulated and the inward rectifier property of Ik1 was weakened during the gradual apoptotic process by 50 μmol/L H2O2 treatment for 24h.
KEY WORDS hydrogen peroxide; potassium; apoptosis; cardiac
myocytes
参考文献:
1. Hughes FM Jr, Bortner CD, Purdy GD, Cidlowski JA. Intracellular K+ suppresses the activation of apoptosis in lymphocytes. J Biol Chem 1997; 272: 30567-76.
2. Yu SP, Yeh CH, Sensi SL, Gwag BJ, Canzoniero LM, Farhangrazi ZS et al. Mediation of neuronal apoptosis by enhancement of outward potassium current. Science 1997; 278: 114-7.
3. Yu SP, Yeh CH, Gottron F, Wang X, Grabb MC, Choi DW. Role of the outward delayed rectifier K+ current in ceramide-induced caspase activation and apoptosis in cultured cortical neurons. J Neuronchem 1999b; 73: 933-41.
4. Hubert h. Nietsch, Michael W. Roe, Jerome F. Fiekers, Ann L. Moore, and Steven D. Lidofsky. Activation of potassium and chloride channels by tumor necrosis factor α. Role in liver cell death. J Biol Chem 2000; 275: 20556-61.
5. Yu SP, Farhangrazi ZS, Ying HS, Yeh CH, Choi DW. Enhancement of outward potassium current may participate in beta-amyloid peptide-induced cortical neuronal death. Neurobiol Dis 1998; 5: 81-8.
