AMHERST, Mass. — Building on their groundbreaking 2018 research into how some of the body's cells, such as neurons and cardiac tissue, communicate via ions that flow through cellular channels, chemists at the University of Massachusetts Amherst demonstrated a "leakiness" to a particularly mysterious type of channel, known as a "big potassium," or BK channel. This leakiness is key to further study the body's electrical infrastructure, which, when it goes haywire, can result in maladies like epilepsy and hypertension.
Instead of electron-carrying wires, electricity flows through our bodies in ion-carrying cellular channels. This is one of the ways that cells communicate with each other. There are hundreds of such channels but the most conductive, and one of the most important, is the BK channel.
While many of the body's other ion channels have hard doors that can open and close, starting and stopping the flow of electricity, BK channels do not. In fact, they appear to be always open, and until recently it was a mystery how these channels could regulate the flows of ions at all—though they were doing just that.
"In 2018, we showed that BK channels have a unique property ," says UMass Amherst Professor of Chemistry Jianhan Chen . Channels are composed of two parts: a filter, and a pore. "The pore of BK is very hydrophobic, or water-repellent," says Chen. "When the channel diameter decreases below a particular threshold, it drives out liquid water and creates a vapor barrier, blocking the flow of potassium ions."
In their newest research, published recently in PRX Life , Chen and his colleague, Zhiguang Jia, a staff scientist in UMass Amherst's chemistry department during the study, demonstrated that the soft, hydrophobic gate regulating the electrical, ionic flows in the BK channels are inherently "leaky," meaning that they cannot absolutely stop the flow of ions. This leakiness is key to further study of the body's electrical infrastructure.
Chen likened the effect to wax paper. "If you drip a drop of water on it, it doesn't absorb but beads up into a droplet. Now roll that wax paper into a tube," he adds, "and you have a BK channel's pore. As long as that tube is wide enough, water can flow through it. But once you narrow it past a certain diameter, the hydrophobic nature of the wax will act as a soft gate, keeping the water out of the tube. This soft gate is a vapor barrier past which it's difficult for water to slip."
Because an ion, such as a potassium ion, is always bound by water, a hydrophobic vapor barrier, by keeping the water out, keeps the potassium ion out, too, effectively shutting off the flow of electricity.
Or at least, that's how it should work.
"We've discovered that this vapor barrier is inherently leaky, determined by the laws of physics," says Chen, meaning that though the BK channel's soft gate can almost always stop the flow of potassium ions, it simply cannot do so 100% of the time—there's always a small probability that ions will slip past. The soft gate is "intrinsically open," even when the channel is supposed to be "fully" closed.
Chen and his coauthor also discovered that the soft gate's leakiness can be influenced by changes, including mutations, to the physical characteristics of the BK channel itself.
Taken together, the research points the way toward a method for understanding how BK channels, and those that function like them, work and malfunction. It's hard to study a vapor barrier, because it is the absence of something that should be there. But the inherent leakiness of such channels can be studied, manipulated in the lab and used as a diagnostic tool for future research into the body's electrical system, the scientists say.
This work was supported by the National Institutes of Health.
