摘要
目的探讨β淀粉样肽25-35(Aβ_(25-35))对海马神经元电压门控的钙通道电流(VGCC)的作用。方法应用全细胞膜片钳技术记录海马神经元上的 VGCC,通过设定不同的钳制电压分别记录高电压激活的钙电流(HVA-I_(Ca))和低电压激活的钙电流(LVA-I_(Ca)),并观察 Aβ_(25-35)对其的影响。结果分别对原代培养的海马神经元急性胞外给予2μmol/L和10μmol/L 的凝聚态 Aβ_(25-35),在最大激活电压下加药后,I_(Ca)幅度分别是加药前的99.80%±0.02%及100.00%±1.58%,差异没有统计学意义。10 μmol/L 凝聚态 Aβ_(25-35)预孵育24 h 可增大,I_(Ca),对照组(未给 Aβ_(25-35))为(24.49±4.35)pA/pF,Aβ_(25-35)组(预孵育24 h)为(46.59±7.15)pA/pF,两组差异有统计学意义(P<0.05);但Aβ_(25-35)组的膜电容[(14.34±1.74)pF]与对照组[(14.44±0.97)pF]相比差异没有统计学意义。结论急性给予凝聚态 Aβ_(25-35)对 VGCC 没有影响,24 h 预孵育凝聚态 Aβ_(25-35)增大了 VGCC,而膜电容没有改变,提示凝聚态 Aβ_(25-35)可通过对细胞膜上钙通道进行分子调控以增大 VGCC。
Objective To investigate the effect of β-amyloid peptide 25-35 （Aβ25-35）on voltagegated Ca^2＋ channel current （VGCC） in primary cultured hippocampal neurons. Methods Whole cell configuration of patch clamp technique was used to record VGCC. High voltage activated calcium current （ HVA-ICa ） was differentiated from low voltage activated calcium current （ LVA-ICa ） by using different levels of holding voltage in primary hippocampal neurons, and the action of Aβ25-35 was examined. Results After acute extracellular exposure 2 μmol/L and 10 μmol/L of Aβ25-35 under maximal activation membrane potential, the amplitude of ICa was 99. 80% ± 0. 02% and 100.00% ± 1.58% of that of the controls, respectively. No significant difference was found after treatment of Aβ25-35. Twenty-four hours pretreatment 10 μmol/L of aggregating Aβ25-35 stimulated an increase in voltage-gated Ca^2＋ channel current （control （24.49 ±4. 35） pA/pF, Aβ25-35 （46. 59 ±7. 15） pA/pF, P 〈0.05） ; However, the membrane capacitance did significantly differ between Aβ group and control group （ Aβ25-35 （ 14. 34 ± 1.74 ） pF, control （ 14. 44 ± 0. 97） pF,P 〉 0. 05 ）. Conclusions Acute extracellular exposure of aggregating Aβ25-35 has no effect on VGCC. Pretreatment of aggregating Aβ25-35 for 24 hours increases VGCC, instead of the membrane capacitance, in primary hippocampal neuron, indicating that molecular modulation of aggregating Aβ25-35 on voltage-gated Ca^2＋ channel results in an increase of VGCC.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2007年第10期659-662,共4页
Chinese Journal of Neurology
基金
福建省重大科技基金(2003F009)
关键词
海马
神经元
淀粉样Β蛋白
肽碎片
钙通道
膜片钳术
Hippocampus
Neuron
Amyloid beta-protein
Peptide fragments
Calcium channels
Patch-clamp techniques
