Discovery of calcium channel mechanism offers clues for brain disorder treatments

DGIST (President Kunwoo Lee) announced that a research team led by Professor Byung Chang Suh of the Department of Brain Sciences has, for the first time, uncovered a novel molecular mechanism that regulates the "N-type voltage-gated calcium channel (CaV2.2)," which plays a critical role in neural signal transmission. By revealing the mechanism that controls how this channel opens and closes, the team has provided an important clue for the future development of therapeutics for brain disorders.

Neurons transmit information to the next cell by converting electrical signals into chemical signals. A critical step in this process is the influx of calcium ions into the cell through voltage-gated calcium channels. Professor Byung Chang Suh's research team uncovered the existence of a so-called "molecular lever" that controls this calcium channel and its regulatory mechanism, providing an important foundation for the development of next-generation therapeutics for brain disorders.

The length of time that the calcium channel remains open varies depending on the type of "beta (β) subunit," an auxiliary protein that binds to the channel. However, the mechanism by which this subunit alters the channel's structure was previously unknown.

Through a comparative analysis of various beta-subunit models, the research team found that a specific region of the channel where the auxiliary protein binds (R370, located at the beginning of the I–II loop) was unusually bent. The team further discovered that this loop pivots around R370 and acts like a "lever," altering the channel's structure at different angles depending on the type of beta subunit bound to it. Accordingly, the team presented the world's first model showing how the movement of this molecular lever changes the calcium channel's structure.

Furthermore, by measuring the channel's open and closed states using electrophysiological techniques and applying kinetic modeling, the research team demonstrated that these structural changes are critical to neuronal signal transmission. This discovery is expected to serve as a new milestone in the development of therapeutics for a wide range of intractable brain disorders involving calcium channels, including neuropathic pain, epilepsy, autism spectrum disorder, and Alzheimer's disease.

Through this study, we clearly elucidated the long-standing question of how beta-subunit binding induces dynamic and structural changes in calcium channels. We expect the newly discovered molecular-lever mechanism of calcium channels to greatly contribute to the future development of new therapeutics for brain disorders."

Professor Byung Chang Suh, Department of Brain Sciences, DGIST

This study was supported by the Basic Research Laboratory, Leading Brain Science Convergence Technology Development, and Core Individual Basic Research programs of the National Research Foundation of Korea. The findings were published in the in the July 2026 issue of the Proceedings of the National Academy of Sciences, with Jin-Nyung Woo, a student in the integrated bachelor's–master's–doctoral program in the Department of Brain Sciences at DGIST, as the first author and researcher Jeongeun Kim as a co-author.