Effects of bound Ts3 on voltage dependence of sodium channel transitions to and from inactivation and energetics of its unbinding
Effects of bound Ts3 on voltage dependence of sodium channel transitions to and from inactivation and energetics of its unbinding
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DOI：
10.1385/cbb:44:3:424
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发表时间：
2006-01-01
影响因子：
2.6
通讯作者：
Beirao, PSL
中科院分区：
文献类型：
--
作者：
Campos, FV;Beirao, PSL
最近，我们提出了一个定量模型来解释的分子机制的Tityus serrulatus Ts 3 α-毒素对钠通道的作用。在该模型中，毒素作为阻止结构域IV的区段S4到达其最外位置的终止物，从而损害正常的快速失活而不影响活化。在目前的工作中，我们分析了所提出的模型的预测与电压依赖性的过渡，从失活。我们的研究结果表明，从失活的恢复是显着更快的Ts 3结合通道，并没有显着的电压依赖性。在Ts 3修饰的通道中从开放状态到失活状态的转变呈现出小但显著的电压依赖性，这可能来自于失活的固有电压依赖性或在结合的Ts 3存在下IVS 4的短移动。我们还研究了TO从其结合位点的电压依赖性位移的热力学参数。我们观察到，去除毒素的活化能为27 kJ/mol，其中一部分来自于施加的去极化电位和0.54 e（0）的等效电荷的移动。这些结果支持所提出的模型。
Recently, we proposed a quantitative model to explain the molecular mechanism of action of the Tityus serrulatus Ts3 alpha-toxin on sodium channels. In this model, the toxin acts as a stop that prevents the segment S4 of domain IV from reaching its outermost position, thus impairing the normal fast inactivation without affecting activation. In the present work, we analyze the predictions of the proposed model with regard to the voltage-dependent transitions to and from inactivation. Our results show that the recovery from inactivation was significantly faster in Ts3-bound channels and that there was no significant voltage dependence. The transition to inactivated state from open state in Ts3-modified channels presented a small but significant voltage dependence, which may derive from an intrinsic voltage dependence of inactivation or by a short movement of IVS4 in the presence of bound Ts3. We also studied the thermodynamic parameters of the voltage-dependent displacement of TO from its binding site. We have observed that the activation energy to remove the toxin is 27 kJ/mol, part of which derives from the imposed depolarizing potential and the movement of an equivalent electrical charge of 0.54 e(0). These results support the proposed model.