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.