Chen H, Heinemann S H
Research Unit Molecular and Cellular Biophysics, Medical Faculty of the Friedrich Schiller University Jena, D-07747 Jena, Germany.
J Gen Physiol. 2001 Jun;117(6):505-18. doi: 10.1085/jgp.117.6.505.
The effects of the scorpion alpha-toxins Lqh II, Lqh III, and LqhalphaIT on human cardiac sodium channels (hH1), which were expressed in human embryonic kidney (HEK) 293 cells, were investigated. The toxins removed fast inactivation with EC(50) values of <2.5 nM (Lqh III), 12 nM (Lqh II), and 33 nM (LqhalphaIT). Association and dissociation rates of Lqh III were much slower than those of Lqh II and LqhalphaIT, such that Lqh III would not dissociate from the channel during a cardiac activation potential. The voltage dependence of toxin dissociation from hH1 channels was nearly the same for all toxins tested, but it was different from that found for skeletal muscle sodium channels (muI; Chen et al. 2000). These results indicate that the voltage dependence of toxin binding is a property of the channel protein. Toxin dissociation remained voltage dependent even at high voltages where activation and fast inactivation is saturated, indicating that the voltage dependence originates from other sources. Slow inactivation of hH1 and muI channels was significantly enhanced by Lqh II and Lqh III. The half-maximal voltage of steady-state slow inactivation was shifted to negative values, the voltage dependence was increased, and, in particular for hH1, slow inactivation at high voltages became more complete. This effect exceeded an expected augmentation of slow inactivation owing to the loss of fast inactivation and, therefore, shows that slow sodium channel inactivation may be directly modulated by scorpion alpha-toxins.
研究了蝎α-毒素Lqh II、Lqh III和LqhalphaIT对在人胚肾（HEK）293细胞中表达的人心脏钠通道（hH1）的影响。这些毒素消除快速失活，其半数有效浓度（EC50）值分别为<2.5 nM（Lqh III）、12 nM（Lqh II）和33 nM（LqhalphaIT）。Lqh III的结合和解离速率比Lqh II和LqhalphaIT慢得多，以至于在心脏动作电位期间Lqh III不会从通道上解离。所有测试毒素从hH1通道解离的电压依赖性几乎相同，但与骨骼肌钠通道（muI；Chen等人，2000年）的情况不同。这些结果表明毒素结合的电压依赖性是通道蛋白的一种特性。即使在激活和快速失活饱和的高电压下，毒素解离仍保持电压依赖性，这表明电压依赖性源自其他来源。Lqh II和Lqh III显著增强了hH1和muI通道的慢失活。稳态慢失活的半数最大电压向负值移动，电压依赖性增加，特别是对于hH1，高电压下的慢失活变得更完全。这种效应超过了由于快速失活丧失而导致的慢失活预期增强，因此表明慢钠通道失活可能直接受到蝎α-毒素的调节。
