Block of single L-type Ca2+ channels in skeletal muscle fibers by aminoglycoside antibiotics
Block of single L-type Ca2+ channels in skeletal muscle fibers by aminoglycoside antibiotics
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DOI：
10.1085/jgp.107.3.421
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发表时间：
1996-03-01
影响因子：
3.8
通讯作者：
Lansman, JB
中科院分区：
文献类型：
--
作者：
Haws, CM;Winegar, BD;Lansman, JB
从小鼠急性分离的骨骼肌纤维上的细胞贴附贴片记录单个L型Ca2+通道的活性。实验涉及氨基糖苷类抗生素抑制离子通过通道的机制。氨基糖苷类产生离散的单通道电流的波动时，添加到外部解决方案。阻断动力学可以描述为氨基糖苷分子和开放通道之间的简单双分子反应。当膜电位负移或外渗透离子浓度降低时，阻断率增加。这两种效应都与位于通道孔内的阻断位点一致。然而，其他功能的块，是不兼容的一个简单的孔阻塞机制。超极化提高了解封率，即使氨基糖苷类分子必须解离从其结合位点的通道朝向外部解决方案对膜领域。提高外渗透离子浓度也能提高解堵率。后者的发现表明，aminglycoside的亲和力被修改的排斥相互作用时出现的孔同时被一个渗透离子和氨基糖苷分子占据。
The activity of single L-type Ca2+ channels was recorded from cell-attached patches on acutely isolated skeletal muscle fibers from the mouse. The experiments were concerned with the mechanism by which aminoglycoside antibiotics inhibit ion flow through the channel. Aminoglycosides produced discrete fluctuations in the single-channel current when added to the external solution. The blocking kinetics could be described as a simple bimolecular reaction between an aminoglycoside molecule and the open channel. The blocking rate was found to be increased when either the membrane potential was made more negative or the concentration of external permeant ion was reduced. Both of these effects are consistent with a blocking site that is located within the channel pore. Other features of block, however, were incompatible with a simple pore blocking mechanism. Hyperpolarization enhanced the rate of unblocking, even though an aminoglycoside molecule must dissociate from its binding site in the channel toward the external solution against the membrane field. Raising the external permeant ion concentration also enhanced the rate of unblocking. This latter finding suggests that aminglycoside affinity is modified by repulsive interactions that arise when the pore is simultaneously occupied by a permeant ion and an aminoglycoside molecule.