Hsu K S
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Neurosci Lett. 1994 Nov 21;182(1):99-103. doi: 10.1016/0304-3940(94)90216-x.
The modulation by endogenous polyamine spermine on acetylcholine (ACh)-induced currents was evaluated using a outside-out patch and whole-cell voltage-clamp recordings from cultured Xenopus muscle cells. Spermine potentiated the ACh-induced whole-cell currents at micromolar concentrations but is less effective at millimolar concentrations at a holding potential of -60 mV. It produced a voltage-dependent potentiation of ACh-induced whole-cell currents; the degree of potentiation by 100 microM spermine was 18.3 +/- 1.7% at a holding potential of -60 mV while 108.2 +/- 2.9% increase at +60 mV. Arcaine, a putative competitive antagonist at the polyamine-binding site on the N-methyl-D-aspartate (NMDA) receptor-channel complex, reduced the spermine enhancement of ACh-induced whole-cell currents. Glycine (10 microM) had no effect on the potentiation of ACh-induced whole-cell currents by spermine. In single-channel recordings, spermine (1 microM to 1 mM) increased the opening frequency of both low- and high-conductance ACh channels and at higher concentrations (> or = 100 microM) it produced, in addition, a voltage-dependent decrease in channel amplitude and average open time of both types of ACh channels that limits its enhancing action. It is likely that these two actions of spermine, due to differences in concentration- and voltage-dependence, are mediated by different binding sites on the nicotinic ACh receptor-channel complex of the muscle cells.
利用从培养的非洲爪蟾肌肉细胞进行的外向膜片钳和全细胞电压钳记录，评估了内源性多胺精胺对乙酰胆碱（ACh）诱导电流的调节作用。在-60 mV的钳制电位下，精胺在微摩尔浓度时增强ACh诱导的全细胞电流，但在毫摩尔浓度时效果较差。它对ACh诱导的全细胞电流产生电压依赖性增强作用；在-60 mV的钳制电位下，100 μM精胺的增强程度为18.3±1.7%，而在+60 mV时增加108.2±2.9%。阿卡因是N-甲基-D-天冬氨酸（NMDA）受体通道复合物上多胺结合位点的一种假定竞争性拮抗剂，它降低了精胺对ACh诱导的全细胞电流的增强作用。甘氨酸（10 μM）对精胺增强ACh诱导的全细胞电流没有影响。在单通道记录中，精胺（1 μM至1 mM）增加了低电导和高电导ACh通道的开放频率，并且在较高浓度（≥100 μM）时，它还使两种类型的ACh通道的通道幅度和平均开放时间出现电压依赖性降低，这限制了其增强作用。由于浓度和电压依赖性的差异，精胺的这两种作用可能是由肌肉细胞烟碱型ACh受体通道复合物上不同的结合位点介导的。
