Lead modulation of the neuronal nicotinic acetylcholine receptor in PC12 cells

被引:11
作者
Nagata, K [1 ]
Huang, CS [1 ]
Song, JH [1 ]
Narahashi, T [1 ]
机构
[1] NORTHWESTERN UNIV,SCH MED,DEPT MOL PHARMACOL & BIOL CHEM,CHICAGO,IL 60611
关键词
lead; heavy metal; nicotinic acetylcholine receptor; ion channel; PC12; cell;
D O I
10.1016/S0006-8993(97)00037-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Lead is known to modulate several ligand- and voltage-gated ion channels, including the nicotinic acetylcholine receptor (AChR) channel. We examined the effects of lead on the nicotinic AChR in rat clonal phaeochromocytoma PC12 cells using whole-cell and single-channel patch-clamp techniques to clarify the detailed mechanism of action. Lead suppressed acetylcholine-induced currents in a dose-dependent manner with an EC50 value of 37 mu M and a Hill coefficient of 0.82. At the single-channel level, 1-10 mu M lead shortened the opening and burst durations, and increased the duration of mean closed time. The open probability was significantly decreased by lead. These changes of single-channel kinetics result in a significant decrease in the total charge carried through the open AChR channels explaining the suppressive effect of lead on acetylcholine-induced whole-cell currents. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:21 / 27
页数:7
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