SO_2代谢衍生物对大鼠海马CA_1区神经元瞬间外向钾电流和延迟整流钾电流的影响  

Effects of SO_2 derivatives on transient outward K^+ and delayed rectifier K^+ currents in acutely isolated rat hippocampal CA_1 neurons

作　　者：桑楠[1] 孟紫强[1] 

机构地区：[1]山西大学环境医学与毒理学研究所,太原030006

出　　处：《动物学报》2003年第1期73-79,共7页ACTA ZOOLOGICA SINICA

基　　金：国家自然科学基金资助项目 (No .30 0 70 6 47)~~

摘　　要：本文利用全细胞膜片钳技术研究了SO2 代谢衍生物———NaHSO3 和Na2 SO3 (二者分子比为 1∶3)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。结果表明 ,SO2 代谢衍生物可显著增大IA 和IK,且呈剂量依赖性关系 ,使IA 和IK 增大 5 0 %的剂量分别为 2 6 19μmol/L和 14 5 0 μmol/L。此外还与电压呈依赖性关系 ,但不具有频率依赖性。结果还表明 ,10 μmol/LSO2 代谢衍生物不影响IA 的激活过程 ,而对IK 的激活过程有非常显著的影响 ,给药前后IK 的半数激活电压分别为 17 6 4± 7 31mV和 13 43± 2 0 0mV (n=10 ,P <0 0 1) ,但不改变其斜率因子。另外 ,10 μmol/LSO2 代谢衍生物还非常显著地影响IA 的失活过程 ,给药前后其半数失活电压分别为 - 6 5 93± 1 97mV和 - 5 9 2 2± 3 83mV (n =10 ,P <0 0 1) ,但不改变其斜率因子。由此推断 ,SO2 代谢衍生物增大大鼠海马CA1区神经元的IA 和IK,促进IK 的激活过程 ,并抑制IA 的失活过程 ,可导致胞内K+ 通过K+ 通道的外流增加 ,胞内K+ 浓度降低 ,造成中枢神经元功能紊乱 ,诱导神经细胞凋亡。这意味着SO2 代谢衍生物对中枢神经系统具有损伤作用 ,从而提示大气SO2 污染可能与一些中枢神经系统疾病的发生以及衰老有关 [动物学报 49(1)In order to investigate possible mechanisms through which SO 2 affects the central neuronal system (CNS), we examined the effects of SO 2 derivatives on the transient outward K+ (I A) and delayed rectifier K+ currents (I K) in freshly dissociated hippocampal CA 1 rat neurons using whole-cell patch clamp techniques. Single rat hippocampal CA 1 neurons were acutely isolated by enzymatic digestion and mechanical dispersion from 7-10-day-old wistar rats. Cells with a pyramidal shaped soma, short dendrites and axons were chosen for study and used within 3 h after dissociation. Whole-cell patch clamp recordings were made with an Axopatch 200B patch clamp amplifier (Axon Instruments, USA); cells were held at a holding potential (HP) of 100 mV and a series of 160 ms depolarizing steps to +90 mV (10 mV increment at each step) were applied at a frequency of 0.5 Hz. Evoked currents were filtered at 2 kHz, digitized at 1.67 kHz, and stored in PC 586 computer using a digidata 1 200B interface (Axon Instruments, USA) and pCLAMP version 6.0.4 software (Axon Instruments, USA). Capacity transients were canceled and series resistance was compensated (>70%) using the internal circuitry of Axopatch 200B. All experiments were conducted at room temperature (20-25℃). All data were analyzed by the use of pCLAMP CLAMPFIT procedures (Axon Instruments) and Origin 5.0 (Microcal software, USA). Results were presented as ±SD, and statistical comparisons were made using Student's t-test. Upon the administration of SO 2 derivatives, the amplitudes of I A and I K were increased incrementally in doses from 1 to 100 μM. Half-increase doses were 26.19 μmol/L and 14.50 μmol/L, respectively. In addition, the increase in the amplitudes of I A and I K was different at different membrane potentials, but was not markedly changed at different frequencies. The results indicate that SO 2 derivatives reversibly increased the amplitudes of I A and I K in a dose-dependent and voltage-dependent, but not frequency-dependent manner. B

关 键 词：SO2代谢衍生物 大鼠 海马 CAl区神经元 瞬间外向钾电流 延迟整流钾电流 全细胞膜片钳技术 

分 类 号：Q424[生物学—神经生物学]