SerpApi.Org
Scientists have, for the first time, mapped in exquisite three-dimensional detail six major conformations of a membrane in the brain related to learning, memory and fear-related behavior.
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The study, led by researchers at Oregon Health & Science University, was published today in Nature Structural & Molecular Biology.
Researchers used state-of-the-art cryo-electron microscopy housed at OHSU's South Waterfront Campus to capture the most detailed view yet of a specific type of membrane protein: an acid-sensing ion channel known as ASIC1a.
The findings could form a blueprint for drug development to treat stroke, said senior author Isabelle Baconguis, Ph.D., assistant professor at the OHSU Vollum Institute.
"Previous studies show that when you block this channel, it can be neuroprotective," Baconguis said. "If you're able to design a drug that delivers an inhibitor to this channel, it could lengthen tissue survival in cases of stroke."
How acidity reveals the channel
Already, scientists in Australia are using a molecule derived from spider venom that explicitly targets ASIC1a to improve outcomes in heart attacks and stroke.
OHSU researchers used recombinant DNA technology to express the human gene and generate human proteins that they imaged using cryo-EM. Because acid-sensing ion channels respond to variations in extracellular pH in the central and peripheral nervous systems, researchers were able to capture six distinct conformations by varying the channels' exposure to acidity.
"In our bodies, there are locations where cells undergo different pH conditions, especially in the brain," Baconguis said. "In neuronal injuries such as stroke, where brain tissue undergoes a drop in pH, these channels can be activated, causing tissue damage."
A blueprint for faster protection
The images provide a blueprint for designing new drugs capable of inhibiting this specific acid-sensing ion channel in cases of stroke.
"The sooner you can protect brain tissue from damage, the less severe the disability stroke survivors will have," Baconguis said. "Time is of the essence when it comes to stroke."
More information: James Cahill et al, Conformational plasticity of human acid-sensing ion channel 1a, Nature Structural & Molecular Biology (2026). DOI: 10.1038/s41594-026-01845-0
Provided by Oregon Health & Science University
This story was originally published on Medical Xpress.
