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目的 比较碘化二甲基粉防已碱 (DMTI)和二氢 - β -刺桐啶碱 (dHβE)对烟碱诱发电流的抑制作用 ,并确定DMTI在烟碱受体上的作用位点。方法 取新生Wistar大鼠骨骼肌细胞体外培养获得肌球 ,用膜片箝全细胞记录技术 ,观察肌球的烟碱诱发电流。结果 0 .0 8mmol·L-1DMTI抑制烟碱诱发电流幅度的作用与 0 .0 2mmol·L-1dHβE的作用类似。向单个细胞持续给烟碱覆盖诱发电流的全过程。电流的衰减过程反映了烟碱受体的失敏 ,DMTI使烟碱诱发电流的慢失敏时间常数减小 ,即加速受体失敏 ,但没发现dHβE有这种作用。在 - 30、- 5 0、- 70、- 90mV钳制电压处观察电压改变对DMTI和对dHβE作用的影响 ,没有发现DMTI或dHβE抑制烟碱电流的作用随钳制电压改变而改变 ,即两者的作用都是非电压依赖性的 ,表明DMTI和dHβE都不是离子通道阻断剂。结论 由于烟碱受体是变构蛋白 ,变构调节剂能加速受体失敏 ,DMTI的抑制作用符合变构调节剂的作用特点 ,并且作用位点不在烟碱受体离子通道 ,而dHβE不是变构调节剂
Objective To compare the inhibitory effects of dimethylstilbestrol (DMTI) and dihydro - β - pyralines (dHβE) on the nicotine - induced currents and to determine the site of action of DMTI on nicotinic receptors. Methods Skeletal muscle cells of neonatal Wistar rats were cultured in vitro and myosotis was harvested. Whole-cell patch-clamp recording technique was used to observe the nicotine-induced currents in myotubes. Results The effect of 0.08 mmol·L-1 DMTI on nicotine-induced current amplitude was similar to that of 0.022 mmol·L-1dHβE. Sustained delivery of nicotine to individual cells induces an electrical current throughout the process. The decay of current reflects the desensitization of nicotinic receptors. DMTI decreases the time constant of nicotine-induced slow desensitization, which accelerates the receptor desensitization, but no effect of dHβE has been found. The effects of voltage changes on DMTI and dHβE were observed at the clamp voltages of -30, -50, -70 and -90mV, and it was found that the effect of DMTI or dHβE on nicotine inhibition varied with the clamp voltage, ie, The effects are both voltage-independent, indicating that both DMTI and dHβE are not ion channel blockers. CONCLUSIONS: Because nicotine receptors are allosteric proteins, allosteric modulators accelerate receptor desensitization. The inhibitory effect of DMTI conforms to the role of allosteric modulators, and the site of action is not in the nicotinic receptor ion channel, whereas dHβE is not Allosteric modulators