Bezanilla F
Departments of Physiology and Anesthesiology, University of California at Los Angeles, School of Medicine, Los Angeles, California 90095, USA.
Physiol Rev. 2000 Apr;80(2):555-92. doi: 10.1152/physrev.2000.80.2.555.
In voltage-dependent Na, K, or Ca channels, the probability of opening is modified by the membrane potential. This is achieved through a voltage sensor that detects the voltage and transfers its energy to the pore to control its gate. We present here the theoretical basis of the energy coupling between the electric field and the voltage, which allows the interpretation of the gating charge that moves in one channel. Movement of the gating charge constitutes the gating current. The properties are described, along with macroscopic data and gating current noise analysis, in relation to the operation of the voltage sensor and the opening of the channel. Structural details of the voltage sensor operation were resolved initially by locating the residues that make up the voltage sensor using mutagenesis experiments and determining the number of charges per channel. The changes in conformation are then analyzed based on the differential exposure of cysteine or histidine-substituted residues. Site-directed fluorescence labeling is then analyzed as another powerful indicator of conformational changes that allows time and voltage correlation of local changes seen by the fluorophores with the global change seen by the electrophysiology of gating currents and ionic currents. Finally, we describe the novel results on lanthanide-based resonance energy transfer that show small distance changes between residues in the channel molecule. All of the electrophysiological and the structural information are finally summarized in a physical model of a voltage-dependent channel in which a change in membrane potential causes rotation of the S4 segment that changes the exposure of the basic residues from an internally connected aqueous crevice at hyperpolarized potentials to an externally connected aqueous crevice at depolarized potentials.
在电压依赖性钠、钾或钙通道中，通道开放的概率会受到膜电位的影响。这是通过一个电压传感器实现的，该传感器检测电压并将其能量传递给孔道以控制其门控。我们在此展示电场与电压之间能量耦合的理论基础，这有助于解释在单个通道中移动的门控电荷。门控电荷的移动构成门控电流。文中描述了这些特性，以及宏观数据和门控电流噪声分析，它们与电压传感器的运作和通道的开放相关。电压传感器运作的结构细节最初是通过诱变实验定位构成电压传感器的残基并确定每个通道的电荷量来解决的。然后根据半胱氨酸或组氨酸取代残基的差异暴露情况分析构象变化。接着分析定点荧光标记，它是构象变化的另一个有力指标，能使荧光团观察到的局部变化与门控电流和离子电流电生理学观察到的整体变化在时间和电压上相关联。最后，我们描述了基于镧系元素的共振能量转移的新结果，这些结果显示通道分子中残基之间的距离有微小变化。所有电生理和结构信息最终汇总在一个电压依赖性通道的物理模型中，其中膜电位的变化会导致S4段旋转，从而使碱性残基的暴露情况从超极化电位下内部相连的水相裂隙转变为去极化电位下外部相连的水相裂隙。
