Scientists have generated structural images of a newly-described class of ion channels that help maintain the balance of pH inside brain cells. These molecular gates, called proton-activated chloride channels (PAC) are critical to the survival of cells and may help prevent disorders like brain injury or stroke. The visualizations have been reported in Nature.
Protein channels sit inside of cell membranes, where they help control the passage of various molecules or ions in and out of cells; PACs regulate the movement of chloride ions. Cells can use these channels to sense and respond to information about their environment.
"Proton-activated chloride channels have only recently been described but they are critical for cell survival, particularly in the brain," said the co-corresponding study author Wei Lü, Ph.D., a Van Andel Institute assistant professor. "Our new images, coupled with our findings into how these channels work, provide much-needed molecular blueprints that will help answer long-standing questions in the field and provide new insights into how these channels may be therapeutically targeted in disease."
The ion channels look a bit like a bouquet and have different parts that can change shape depending on the pH of their environment. If the pH changes from basic to acidic, for example, a pH sensor on the channel can move from a state of rest into a co-called acidic pocket; that signals to the gate that it should be open and ions should be allowed to pass in or out of the cell. This work is the first to describe this mechanism.
This data may help researchers understand how these channels affect human health and disease.