焦亚硫酸钠对大鼠海马CA1区神经元钠电流的影响

Effects of sodium metabisulfite on sodium current in acutely isolated rat hippocampal CA1 neurons

目的:探讨SO2及其体内衍生物(亚硫酸盐和亚硫酸氢盐)对中枢神经元钠通道的影响。方法:采用全细胞膜片钳技术研究了焦亚硫酸钠(SMB)对大鼠海马CA1区神经元钠电流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。结果:①焦亚硫酸钠可剂量依赖性地增大全细胞钠电流,剂量为2μmol/L和20μmol/L时,钠电流分别增大(22.36±3.28)%和(65.05±5.75)%(n=10)。②10μmol/L的焦亚硫酸钠不影响钠电流的激活过程,却非常显著地影响其失活过程,使失活曲线显著右移,作用前后的半数失活电压分别为(-82.38±0.54)mV和(-69.39±0.41)mV(n=10,P<0.01),但失活曲线的斜率因子未见改变。③SOD(1×106U/L)、CAT(2×106U/L)及GPx(1×104U/L)均可使SMB(10μmol/L)增大的钠电流部分恢复。结论:SMB增大钠电流并抑制其失活过程,从而影响神经细胞的兴奋性,这一效应可能与硫中心或氧中心自由基的损伤作用有关。

AIM： To study the effects of sodium metabisulfite （SMB）, sulfur dioxide （SO2） and its derivatives in vivo, sodium bisulfite and sulfite, on Na^＋ currents. The effects of superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GPx） against SMB were also studied in freshly dissociated hippocampal CAI neurons in rats. METHODS： The whole- cell patch - clamp techniques were used in the experiments. RESULTS： ① SMB increased the voltage - activated Na^＋ currents in a concentration - and voltage - dependent manner. The amplitudes of Na＋ currents was increased （22.36 ± 3.28） % and （65.05 ± 5.75 ） % （ n = 10） by SMB at 2 μmol/L and 20μmol/L, respectively. ② SMB （ 10μmol/L） did not affect the activation process, but changed the inaetivation process significantly. Before and after application of 10μmol/L SMB, the half- inactivation voltage was （ - 82.38 ± 0.54） mV and （ - 69.39 ± 0.41 ） mV （ n = 10, P 〈 0.01 ）. However, the slope factor remained unchanged. ③ SOD, CAT and GPx partly irdaibited the incremental effect of SMB on Na^＋ currents. CONCLUSION： SMB increases Na^＋ currents and inhibits the steady - state inactivation, which contributes to the increase in the excitibillty of neuronal cells. Its mechanism may involve oxidative damage caused by sulfur- and oxygen - centered free radicals in the rat hippocampal CAI neurons.