Terahertz Wave Enhances Permeability of the Voltage-Gated Calcium Channel

摘要

A deficiency of Ca~(2+) 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~(2+) transport to the calcium channel, we demonstrate the importance of bridging Ca~(2+) hydration waters, which form hydrogen bonds with channel -COO~- and - C=O groups and enable a longdistance effect on the Ca~(2+) 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~(2+). The Ca~(2+) 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~(2+) deficiency in degraded calcium channels, inducing apoptosis of tumor cells with overloaded calcium etc.