The operating principle of proton-activated chloride channels revealed

A research team led by Professor Seo Byeong-Chang from the Department of Brain Sciences at DGIST has made the world’s first discovery of the functioning of proton-activated chloride (PAC) channels, which play an important role in protecting cells in our body. PAC channels are important mediators of cellular damage caused by tissue acidification, and by unraveling the mystery of their activation, the research team has opened up a new avenue for treating cancer and brain diseases.

The study is published in the journal Nature Communications.

Our bodies become acidic when we exercise for long periods of time or when we are ill. This can damage cells. In particular, when the balance of intracellular chloride ions (Cl^–) is disrupted, edema, or swelling of cells, occurs, which can damage cells and tissues. To prevent cell damage, Professor Seo’s research team has been studying how PAC channels work and is now on the verge of developing new treatments.

PAC channels are activated in response to an acidic extracellular environment, i.e., a high concentration of protons (H⁺). Until now, however, researchers did not have a good understanding of how the activation of PAC channels is regulated in cells. A thorough study was needed to solve this problem.

Professor Seo’s research team discovered that activation of PAC channels requires a substance called PI(4,5)P₂ Chloride ions are found inside the cell membrane. Without this substance, PAC channels barely function and the movement of chloride ions is reduced, which prevents cell damage. By elucidating this process, the research team revealed the principle that governs the functioning of PAC channels.

This study is important because it has helped unlock the secret of exactly how PAC channels work. This discovery should help develop new treatments to inhibit cell damage in diseases such as cancer and brain diseases.

“We have identified the regulatory mechanism of PAC channels, which has received relatively little attention,” said Professor Seo. “The working principle of PAC channels that we discovered through this study is expected to be very useful in preventing cell damage in diseases such as cancer and stroke.”

The first author of this study is Dr. Go Woori from the Department of Brain Sciences, DGIST, and co-authors are Lee Eun-ah, a PhD student, and Dr. Lim Hyun-ho from the Korea Brain Research Institute.