Terahertz waves promote Ca²⁺ transport in the Ca_v2.1 channel

Ca_V2.1 channels are the structural foundation for neurotransmitter transmission and other vital biological processes. If autoimmune-mediated reduction in presynaptic Ca_V2.1 leads to a decrease in calcium influx during a presynaptic action potential, which decreases chemical neurotransmission, leading to a debilitating neuromuscular weakness, also known as Lambert-Eaton myasthenia syndrome. The selectivity filter is a core structural component of Ca_V2.1 channels, with a pivotal role in regulating the selective permeation of Ca²⁺ ions. Due to the vibration and rotation frequencies of the selectivity filter of Ca_V2.1 being located in the terahertz band, terahertz waves at specific frequencies may resonate with it, thereby affecting Ca²⁺ current passing through Ca_V2.1. Therefore, it is highly worthwhile to study how the terahertz waves regulate the Ca_V2.1 channel. In this study, we investigate the structure of Ca_V2.1 channels using molecular dynamics simulations. The effect of external terahertz waves on the channel has been examined at different resonant frequencies of the selectivity filter. We found that when the frequency of terahertz waves applied is around the symmetrical vibration frequency of the carboxyl group in the selectivity filter, the PMF of Ca_V2.1 significantly decreases, promoting the transport of Ca²⁺ ions through Ca_V2.1. The reason behind this is that the terahertz waves resonate with the carboxyl groups of the selectivity filter, affecting the hydrogen network between the hydrated water of Ca²⁺ ions and the selectivity filter. These findings open up new treatment avenues for channel diseases such as Lambert-Eaton myasthenic syndrome treated with terahertz waves.