Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane
Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane
复制标题
DOI：
10.1073/pnas.0810187105
复制
发表时间：
2008-12-09
影响因子：
11.1
通讯作者：
MacKinnon, Roderick
中科院分区：
文献类型：
--
作者：
Schmidt, Daniel;MacKinnon, Roderick
电压依赖性K+（Kv）通道通过由膜电压驱动的门控构象变化而成为动作电位的基础。在这项研究中的桨嵌合体KV通道，我们表明，通道开放的速率，开放概率的电压依赖性，和最大可实现的开放概率取决于脂质膜环境。电压传感器毒素VsTx1通过分配到膜中并结合到通道上来干扰电压依赖性门控，其活性也依赖于膜。影响通道功能的膜环境因素可分为两大类：脂质组成和机械状态。机械状态可以对电压依赖性K+通道的功能具有令人惊讶的大影响，包括其与电压传感器毒素的药理学相互作用。VSTx1活性对膜的机械状态的依赖性使我们假设电压传感器毒素通过干扰通道和膜之间存在的相互作用力来发挥其作用。
Voltage-dependent K+ (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K+ channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane.