对河豚毒素敏感和对河豚毒素耐受的钠离子通道对镉离子和锌离子的敏感性不同。

Tetrodotoxin-sensitive and tetrodotoxin-resistant Na+ channels differ in their sensitivity to Cd2+ and Zn2+.

作者信息

Frelin C, Cognard C, Vigne P, Lazdunski M

出版信息

Eur J Pharmacol. 1986 Mar 18;122(2):245-50. doi: 10.1016/0014-2999(86)90109-3.

Abstract

The sensitivity of Na+ channels to inhibition by Cd2+ and Zn2+ was studied in 22Na+ uptake experiments after stabilization of an open conformation of the Na+ channels with different neurotoxins and in voltage clamp experiments. Six different cell types of neuronal, cardiac or skeletal muscle origin were surveyed. Three cell types possess Na+ channels that are highly sensitive to tetrodotoxin (TTX) (Kd = 1-5 nM) and three possess Na+ channels that are resistant to TTX (Kd = 0.3-1 microM). The 22Na+ uptake experiments using veratridine or batrachotoxin to activate Na+ channels indicated that TTX-resistant Na+ channels are more sensitive to the inhibitory action of Cd2+ (IC50(Cd2+) = 0.2 mM) and of Zn2+ (IC50(Zn2+) = 50 microM) than TTX-sensitive Na+ channels (IC50(Cd2+) = 5 mM, IC50(Zn2+) = 2 mM). Electrophysiological experiments showed that high concentrations of Cd2+ (IC50 = 2 mM) are necessary to inhibit both TTX-sensitive and TTX-insensitive Na+ channels when the channels are activated by voltage steps. The results suggest that Cd2+ acts competitively with veratridine or batrachotoxin and that the difference in the effects of Cd2+ and Zn2+ on 22Na+ fluxes in TTX-sensitive and TTX-resistant cells is related to differences at the site of action of alkaloid neurotoxins.

摘要

在利用不同神经毒素使钠通道稳定于开放构象后的²²Na⁺摄取实验以及电压钳实验中，研究了钠通道对Cd²⁺和Zn²⁺抑制作用的敏感性。对六种不同类型的神经元、心脏或骨骼肌来源的细胞进行了检测。其中三种细胞类型的钠通道对河豚毒素（TTX）高度敏感（Kd = 1 - 5 nM），另外三种细胞类型的钠通道对TTX具有抗性（Kd = 0.3 - 1 μM）。使用藜芦碱或蟾毒素激活钠通道的²²Na⁺摄取实验表明，与TTX敏感的钠通道（IC50(Cd²⁺) = 5 mM，IC50(Zn²⁺) = 2 mM）相比，TTX抗性的钠通道对Cd²⁺（IC50(Cd²⁺) = 0.2 mM）和Zn²⁺（IC50(Zn²⁺) = 50 μM）的抑制作用更敏感。电生理实验表明，当通过电压阶跃激活通道时，高浓度的Cd²⁺（IC50 = 2 mM）才能同时抑制TTX敏感和TTX不敏感的钠通道。结果表明，Cd²⁺与藜芦碱或蟾毒素存在竞争性作用，并且Cd²⁺和Zn²⁺对TTX敏感和TTX抗性细胞中²²Na⁺通量影响的差异与生物碱神经毒素作用位点的差异有关。