UMR 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Centre National de Recherche Scientifique-Nancy University, Nancy cedex, France.
Biophys J. 2010 Nov 3;99(9):L72-4. doi: 10.1016/j.bpj.2010.08.069.
The effects on the structural and functional properties of the Kv1.2 voltage-gated ion channel, caused by selective mutation of voltage sensor domain residues, have been investigated using classical molecular dynamics simulations. Following experiments that have identified mutations of voltage-gated ion channels involved in state-dependent omega currents, we observe for both the open and closed conformations of the Kv1.2 that specific mutations of S4 gating-charge residues destabilize the electrostatic network between helices of the voltage sensor domain, resulting in the formation of hydrophilic pathways linking the intra- and extracellular media. When such mutant channels are subject to transmembrane potentials, they conduct cations via these so-called "omega pores." This study provides therefore further insight into the molecular mechanisms that lead to omega currents, which have been linked to certain channelopathies.
本研究采用经典分子动力学模拟，研究了电压门控离子通道 Kv1.2 的电压传感器结构域残基选择性突变对其结构和功能特性的影响。在实验鉴定了参与状态依赖型 ω 电流的电压门控离子通道突变后，我们观察到 Kv1.2 的开放和关闭构象中，S4 门控电荷残基的特定突变会破坏电压传感器结构域螺旋之间的静电网络，导致形成连接细胞内外介质的亲水性途径。当这些突变通道受到跨膜电位时，它们会通过这些所谓的“ω 孔”传导阳离子。因此，本研究进一步深入了解了导致与某些通道病相关的 ω 电流的分子机制。
