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机构地区:[1]山西大学环境医学与毒理学研究所,山西太原030006
出 处:《中国应用生理学杂志》2005年第3期241-246,共6页Chinese Journal of Applied Physiology
基 金:国家自然科学基金重点项目(30230310);国家自然科学基金面上基金项目(20477023)
摘 要:目的:探讨焦亚硫酸钠(SMB)、二氧化硫(SO2)及其体内衍生物(亚硫酸盐和亚硫酸氢盐)对中枢神经元钾通道的影响及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)及谷胱甘肽过氧化物酶(GPx)相应的保护作用。方法:采用全细胞膜片钳技术研究了SMB对大鼠海马CA1区神经元瞬间外向钾电流(IA)和延迟整流钾电流(IK)的影响。结果:①焦亚硫酸钠可增大全细胞IA和IK,且具剂量依赖性和电压依赖性,使IA和IK增大50%的剂量分别为15.8μmol/L和11.5μmol/L;②10μmol/L的SMB均可显著影响IA和IK的激活过程,给药前后IA的半数激活电压分别为(-12.6±1.6)mV和(-7.0±1.3)mV(n=8,P<0.01),IK的半数激活电压分别为(10.8±0.9)mV和(21.6±0.7)mV(n=8,P<0.01),但不改变其斜率因子;③10μmol/L的SMB还非常显著地影响IA的失活过程,给药前后其半数失活电压分别为(-97.0±1.1)mV和(-84.4±3.3)mV(n=8,P<0.01),但也不改变其斜率因子;④抗氧化酶SOD(1×106U/L)、CAT(2×106U/L)及GPx(105U/L)均可使SMB(10μmol/L)增大的IA和IK部分恢复。结论:SMB可显著增大IA和IK,抑制IA和IK的激活过程及IA的失活过程,从而导致胞内K+的外流增加,使胞内K+浓度降低,从而对中枢神经元功能产生不利影响。Aim: To investigate the effects of sodium metabisulfite(SMB), sulfur dioxide(SO2) and its derivatives in vivo, sodium bisulfite and sulfite on K^+ channels of the central neurons and its mechanisms. Methods: By using whole-cell patch-clamp techinique, the effects of SMB on transient outward K^+ (IA) and delayed rectifier K^+ currents(IK) were observed. Results: ① SMB can increase the amplitudes of IA and IK in a dose-dependent and vohage-dependent manner. Their half-increase doses were 15.8 μmol/L and 11.5 μmol/L respectively. ② SMB( 10 μmol/L) significantly shifted the activation curves of IA and IK to more positive potentials. Before and after application of 10μmol/L SMB , the half-activation voltages of IA and IK were ( - 12.6 ± 1.6)mV and ( - 7.0 ± 1.3)mV, (10.8 ± 0.9)mV and (21.6 ± 0.7)mV( P〈 0.01, n = 8), respectively, but the slope factors were not changed. ③ The inactivation curve of IA was shifted to positive potentials, the half-inactivation voltage of IA were( - 97.0 ± 1.1)mV and( - 84.4 ± 3.3)mV ( P 〈 0.01, n = 8) before and after application of SMB( 10μmol/L) , without changing the slope factors. ④ SOD, CAT and GPx could partly inhibit the incremental effect of SMB on IA and IK. Conclusion: SMB, SO2 and its derivatives in vivo, sodium bisulfite and sulfite have the damage effects on the central nervous system, and they can cause extracelluar K+ increase and induce the disturbance of the central neuronal functions. Its mechanism may involve oxidation damage in the rat hippocampal CA1 neurons, caused by sulfurand oxygen-centered free radicals formed in the process of sulfite or bisulfite oxidation.
关 键 词:海马神经元 全细胞膜片钳技术 焦亚硫酸钠 二氧化硫 瞬间外向钾电流(IA) 延迟整流钾电流(IK)
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