Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, People's Republic of China.
Key Laboratory of Physical Electronics and Devices of the Ministry of Education, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.
J Am Chem Soc. 2021 Mar 24;143(11):4311-4318. doi: 10.1021/jacs.0c09401. Epub 2021 Feb 24.
A deficiency of Ca fluxes arising from dysfunctional voltage-gated calcium channels has been associated with a list of calcium channelopathies such as epilepsy, hypokalemic periodic paralysis, episodic ataxia, etc. Apart from analyzing the pathogenic channel mutations, understanding how the channel regulates the ion conduction would be instructive to the treatment as well. In the present work, in relating the free energetics of Ca transport to the calcium channel, we demonstrate the importance of bridging Ca hydration waters, which form hydrogen bonds with channel -COO and -C═O groups and enable a long-distance effect on the Ca permeation. By firing a terahertz wave which resonates with the stretching mode of either the -COO or the -C═O group, we obtain significantly enhanced selectivity and conductance of Ca. The Ca free energy negatively grows nearly 5-fold. The direct evidence is the reinforced hydrogen bonds. In addition, thanks to forced vibrations, -COO contributes to raised permeation as well even under a field in resonance with -C═O, and vice versa. Since the resonant terahertz field could manipulate the conduction of calcium channels, it has potential applications in therapeutic intervention such as rectifying a Ca deficiency in degraded calcium channels, inducing apoptosis of tumor cells with overloaded calcium etc.
钙通道功能障碍导致的钙通量不足与一系列钙通道病有关,如癫痫、低钾周期性麻痹、发作性共济失调等。除了分析致病通道突变外,了解通道如何调节离子传导对于治疗也具有指导意义。在本工作中,我们将 Ca 转运的自由能与钙通道联系起来,证明了桥连 Ca 水合水的重要性,这些水合水与通道的 -COO 和 -C=O 基团形成氢键,并对 Ca 渗透产生长程影响。通过发射与 -COO 或 -C=O 基团的伸缩模式共振的太赫兹波,我们获得了 Ca 显著增强的选择性和电导率。Ca 的自由能几乎降低了 5 倍。直接的证据是氢键的增强。此外,由于强制振动,-COO 即使在与 -C=O 共振的场下也有助于提高渗透,反之亦然。由于共振太赫兹场可以控制钙通道的传导,它在治疗干预方面具有潜在的应用,例如纠正降解钙通道中的钙缺乏,诱导钙超载的肿瘤细胞凋亡等。