Isochannels and Blocking Modes of Voltage‐Dependent Sodium Channels a
Isochannels and Blocking Modes of Voltage‐Dependent Sodium Channels a
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电压依赖性钠通道的等通道和阻断模式
DOI：
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发表时间：
1986
影响因子：
5.2
通讯作者：
J. Heiny
中科院分区：
文献类型：
--
作者：
E. Moczydlowski;A. Uehara;Xiaotao Guo;J. Heiny
我们的结果支持存在三种不同的钠通道亚型或等通道。这些等通道可以很容易地被区分为哺乳动物脑、骨骼肌和心肌中的主要钠通道类型。对魔芋毒素GIIIA和河豚毒素的敏感性足以对这些通道进行分类。骨骼肌通道对河豚毒素和芋螺毒素都非常敏感，脑通道对河豚毒素敏感，而对芋毒素不敏感，心脏和失神经肌肉通道对这两种毒素都不敏感。除了在鸟粪毒素的外部受体部位阻断外，还可以推广到巴曲霉毒素激活的钠通道的其他几种阻断模式。到目前为止，我们对苯佐卡因和普鲁卡因的研究代表了某些疏水分子特有的一种模式。这些分子诱导离散的阻断事件，停留时间随着麻醉剂浓度的增加而明显增加，阻断频率随着负电压的增加而增加。这种模式与带电有机分子的快速内部阻挡非常不同，后者随着正电压的增加而增加。这些结果表明，不可能像Hille先前提出的那样，将局麻药的不同作用归因于内通道口的单一部位。因此，我们的观察支持了其他工作人员的结论，他们使用了两种局麻药的混合物，表明剂量-反应行为不符合单一部位的行为，但需要至少两个不同的部位。对于通道内口和外口的阳离子的相互作用，可以区分两种额外的阻塞模式。有机分子显然可以从通道的内部进入电场，但不能从通道的外部进入。这一结果表明，进入电场的内部途径很宽，外部收缩阻止具有单一甲基的分子进入，但允许二价无机阳离子，如钙离子和Co2+进入。
Our results support the existence of three different Na-channel subtypes or isochannels. These isochannels can be readily distinguished as the predominant Na-channel types in mammalian brain, skeletal muscle, and cardiac muscle. The sensitivity to mu-conotoxin GIIIA and tetrodotoxin is sufficient to classify these channels. The skeletal muscle channel is very sensitive to both tetrodotoxin and mu-conotoxin, the brain channel is sensitive to tetrodotoxin but insensitive to mu-conotoxin, and the heart and denervated muscle channels are insensitive to both toxins. In addition to block at the external receptor site for guanidinium toxins, several other blocking modes can be generalized for batrachotoxin-activated Na channels. One mode is peculiar to certain hydrophobic molecules so far represented by our studies of benzocaine and procaine. These molecules induce discrete blocking events with dwell times that apparently increase with anesthetic concentration and a blocking frequency that increases with negative voltage. This mode is quite distinct from the fast internal block by charged organic molecules that increases with positive voltage. These results imply that it is not possible to ascribe the diverse effects of local anesthetics to a single site in the interior channel mouth, as previously proposed by Hille. Our observations thus support the conclusions of other workers who used mixtures of two local anesthetics to show that the dose-response behavior does not fit single-site behavior, but requires at least two distinct sites. Two additional blocking modes can be distinguished for the interactions of cations at the internal and external mouths of the channel. Organic molecules can apparently enter the electric field from the internal but not the external side of the channel. This result suggests a wide internal entry way to the field and an external constriction that prevents the entry of molecules with a single methyl group but permits entry of divalent inorganic cations such as Ca2+ and Co2+.
单只大鼠心肌细胞中的钠电流。
DOI：
10.1113/jphysiol.1981.sp013879
发表时间：
1981
期刊：
The Journal of physiology
影响因子：
--
作者：
Brown,AM;Lee,KS;Powell,T
通讯作者：
Powell,T
正常和胺菊酯修饰的单钠通道的电压依赖性钙阻断。
影响因子：
3.4
作者：
Yamamoto,D;Yeh,JZ;Narahashi,T
通讯作者：
Narahashi,T