Researchers have applied Nobel prize-winning microscope technology to uncover an ion channel structure that could lead to new treatments for kidney stones . The study was published in  Nature Structural and Molecular Biology , revealed atomic-level of the protein that serves as a passageway for calcium across the kidney cell membranes.

Approximately 80% of kidney stones are comprised of calcium salts. They are extremely painful to pass, and depending on size and location can require surgery to remove. Ion channels that span kidney cell membranes help reabsorb calcium from the urine before it can form kidney stones.

The new study is the first to show molecular details of the essential kidney calcium channel, called TRPV5 , in its closed form. The study also reveals how inhibitor molecules attach to and close the channel, leaving calcium stranded in the urine where it can form kidney stones.

In the new study, Hughes and colleagues used a technique called cryo-electron microscopy  to view rabbit TRPV5 attached to its inhibitor molecule, econazole. Cryo-electron microscopy enabled the researchers to zoom in and see protein structures in atomic details.

From the new vantage point they could identify different protein regions, including the portion that crosses kidney cell membranes, and attachment sites for molecules like econazole.

"When performing cryo-electron microscopy, we shoot electrons at our frozen protein and it allows us to take pictures of individual protein molecules." With these pictures and advanced computer software we are able to create 3D models of these molecules. potential to be so precise that we can actually see the atoms that make up the protein, "Hughes explained.

The 3D models helped the researchers predict how TRPV5 opens and closes for the first time. "To understand how to protein moves we need multiple structures to compare to one another," Hughes said. They were able to draw conclusions about the mechanisms of action by comparing our inhibitor-bound structure to a previous published TRPV6 structure solved without an inhibitor TRPV5 and TRPV6 are part of the same subfamily of proteins and similar in sequence as well as structure.

The researchers viewed TRPV5-econazole complexes under the 12-foot tall cryo-electron microscope housed at the Electron Imaging Center for NanoMachines. Vera Moiseenkova-Bell senior author on the study, has access to this facility as a member of the West / Midwest consortium for high-resolution cryo-electron microscopy supported by the National Institutes of Health. 

Hughes said, "This is the first time the structure of TRPV5 has been solved. Now, structures for four of the TRPV subfamily members are available at near-atomic resolution for further scientific research." According to the researchers, future studies could include targeted therapies to modulate the protein channels in people suffering from kidney stones .