Influence of negative surface charge on toxin binding to canine heart Na channels in planar bilayers.
Influence of negative surface charge on toxin binding to canine heart Na channels in planar bilayers.
复制标题
负表面电荷对毒素与平面双层中犬心脏 Na 通道结合的影响。
DOI：
10.1016/s0006-3495(89)82813-9
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发表时间：
1989
影响因子：
3.4
通讯作者：
Moczydlowski,E
中科院分区：
文献类型：
--
作者：
Ravindran,A;Moczydlowski,E
通过分析犬心脏钠离子通道毒素阻滞的动力学，揭示了犬心脏钠离子通道在河豚毒素/蛤蚌毒素结合位点附近存在负电荷。当[NaCl]在0.05 ~ 3 m范围内变化时，毒素结合的电压依赖性和毒素的解离率基本不变，而毒素的结合速率常数与[NaCl]呈负相关，二价毒素（石蛤毒素2+）的结合速率比一价毒素（河蟹毒素1+）受影响更大。这些关于犬心脏毒素不敏感钠通道的结果与先前关于犬大脑毒素敏感钠通道的发现相似。Green等人的模型（Green， W. N.， L. B. Weiss, and O. S. Anderson. 1987）。J. Gen. Physiol. 89:873-903)，其中包括Na+竞争和表面电荷的Gouy-Chapman筛选，提供了非常适合的数据。结果表明，两种犬钠通道亚型具有相似的表面负电荷密度（1 e-/400 A2）和相似的毒素结合位点Na+竞争解离常数（0.5 M）。因此，负表面电荷是这两种亚型通道函数的保守特征。毒素结合亲和力的差异源于内在关联和解离速率的微小差异。
The presence of negative surface charge near the tetrodotoxin/saxitoxin binding site of canine heart Na channels was revealed by analysis of the kinetics of toxin block of single batrachotoxin-activated Na channels in planar bilayers as a function of [NaCl]. The voltage-dependence of toxin binding and the toxin dissociation rate are nearly constant as [NaCl] is varied from 0.05 to 3 M. In contrast, the association rate constant of the toxins is inversely dependent on [NaCl], with the rate for the divalent toxin, saxitoxin2+, affected more steeply than that of the monovalent toxin, tetrodotoxin1+. These results for toxin-insensitive Na channels from canine heart parallel previous findings for toxin-sensitive Na channels from canine brain. The model of Green et al. (Green, W. N., L. B. Weiss, and O. S. Anderson. 1987. J. Gen. Physiol. 89:873–903), which includes Na+ competition and Gouy-Chapman screening of surface charge, provided an excellent fit to the data. The results suggest that the two canine Na channel subtypes have a similar density of negative surface charge (1 e-/400 A2) and a similar dissociation constant for Na+ competition (0.5 M) at the toxin binding site. Thus, negative surface charge is a conserved feature of channel function of these two subtypes. The difference in toxin binding affinities arises from small differences in intrinsic association and dissociation rates.