Regulation of Ion Permeation of the KcsA Channel by Applied Midinfrared Field

Abstract

Ion transport molecules are involved in many physiological and pathological processes and are considered potential targets for cancer treatment. In the large family of ion transport molecules, potassium (K) ion channels, as surface-expressed proteins, show the highest variability and most frequent expression changes in many tumor types. The key to exploring the permeation of K+ through potassium channels lies in the conserved sequence TVGYG, which is common in the selectivity filter (SF) region of all potassium channels. We found that the K+ flux significantly increased with the help of a specific frequency terahertz electromagnetic wave (51.87 THz) in the KcsA channel using a molecular dynamics combined model through the combined simulation of the constant electric field method and ion imbalance method. This frequency has the strongest absorption peak in the infrared spectrum of -C=O groups in the SF region. With the applied electric field of 51.87 THz, the Y78 residue at the S1 site of the SF has a smaller vibration amplitude and a more stable structure, which enables the K+ to bind closely with the carbonyl oxygen atoms in the SF and realize ion conduction in a more efficient direct Coulomb knock-on.

Computational methods for unlocking the secrets of potassium channels: Structure, mechanism, and drug design

“…In 2018, Kopec et al 87 performed Brownian dynamics simulations on KcsA and found that the energy distribution caused by Coulomb interactions in the "hard knock-on" model may be the reason for its higher ion permeability than the water-mediated "soft knock-on" model. 175 Furthermore, Oiki et al 176,177 revealed that varying solution concentrations affect the distribution of potassium ions in the SF region, leading to the identification of a new conduction mechanism known as the "sparse ion array" model. The de Groot group applied MD simulation and the Markov state model (MSM) to study the influence of different factors such as potassium ions concentration, temperature, and membrane potential on the ion conduction and permeation process in MthK and observed that the infiltration mode is still a "hard knock-on" model, and no water infiltration phenomenon was observed.…”

“…This result verified the “hard knock‐on” model from the computational perspective. In 2018, Kopec et al 87 performed Brownian dynamics simulations on KcsA and found that the energy distribution caused by Coulomb interactions in the “hard knock‐on” model may be the reason for its higher ion permeability than the water‐mediated “soft knock‐on” model 175 . Furthermore, Oiki et al 176,177 revealed that varying solution concentrations affect the distribution of potassium ions in the SF region, leading to the identification of a new conduction mechanism known as the “sparse ion array” model.…”

Effect of THz Waves of Different Orientations on K+ Permeation Efficiency in the KcsA Channel

“…They argued that the mechanism that occurs during the transport of K + is related to its concentration in the system, that the higher the concentration of K + the fewer water molecules there will be at the SF site, and that there should not be a single permeation mechanism [ 26 ]. In our previous work, we found that the direct Coulomb knock-on mechanism is the most efficient for the transport rate of K + and is the dominant permeation mechanism throughout the simulation [ 27 ].…”

“…Stimulation of calcium channels by 42.55 THz EM waves can significantly enhance the selectivity and conductivity of calcium ions, thereby correcting the calcium current reduction caused by calcium channel defects [ 33 ]. In our previous work, a THz field with a frequency of 51.87 THz incident along the direction of the ion flow can significantly the K + flow in the KcsA channel, thus inducing rapid apoptosis of tumor cells with potassium overload [ 27 ].…”

“…In our previous work, we can see that when the frequency of the applied electric field is 51.87 THz, the ion flux of the potassium channel is significantly enhanced, and in addition, the incident direction of the applied electric field is along the direction of the ion current. In practice, it is difficult for us to just add THz waves in a particular direction of a channel [ 27 ]. In this paper, we verify the effects of 51.87 THz electromagnetic waves in different directions on the ion flux of the KcsA channel and further explore the mechanism of THz waves on the KcsA channel.…”