The Unveiling of Nature's Electrical Mysteries
AMHERST, Mass. — In a remarkable continuation of their pioneering research from 2018 (https://www.nature.com/articles/s41467-018-05970-3), scientists at the University of Massachusetts Amherst have recently shed light on the enigmatic behavior of a special type of ion channel in our bodies known as the "big potassium" or BK channel. Their findings reveal a fascinating characteristic—leakiness—that plays a crucial role in understanding the complex electrical systems within our bodies. When these systems malfunction, they can lead to serious health issues such as epilepsy and hypertension.
Unlike traditional electrical systems that rely on wires to carry electrons, our bodies transmit electrical signals through ion channels that transport charged particles. This is a vital mechanism for cellular communication. Among the hundreds of different types of ion channels present in the body, BK channels are particularly significant due to their high conductivity and essential functions.
While many ion channels have tightly controlled mechanisms that open and close like doors to manage ion flow, BK channels operate differently. They seem to be perpetually open, which raised questions about how they could still regulate ion flows effectively. Until recently, this was a mystery that baffled scientists.
According to Jianhan Chen, a Professor of Chemistry at UMass Amherst, "In 2018, we established that BK channels possess a unique property (https://www.nature.com/articles/s41467-018-05970-3)." He explains that these channels consist of two main components: a filter and a pore. The BK channel’s pore is notably hydrophobic, meaning it repels water. "When the diameter of the channel narrows below a certain point, it expels liquid water, forming a vapor barrier that restricts the passage of potassium ions, thereby regulating their flow."
In their latest study, published recently in PRX Life (https://journals.aps.org/prxlife/abstract/10.1103/m89c-6vv7), Chen and his colleague Zhiguang Jia, who contributed as a staff scientist during the research, demonstrated that the soft, hydrophobic gate that governs the ionic flows in BK channels is inherently "leaky." This means that although it generally functions to stop ion flow, it cannot completely prevent ions from passing through. This leakiness is fundamental for advancing our understanding of the body's electrical framework.
To illustrate this effect, Chen likens it to wax paper. "If a drop of water lands on wax paper, it beads up rather than soaking in. Now, if you roll that wax paper into a tube, you create a representation of a BK channel's pore. As long as the tube is sufficiently wide, water can flow through it. However, if you narrow the tube beyond a certain diameter, the wax's hydrophobic quality acts as a soft gate, preventing water from entering the tube. This soft gate creates a vapor barrier that makes it challenging for water to pass through."
Given that ions such as potassium are always associated with water molecules, this vapor barrier not only blocks water but also restricts potassium ions from flowing through, effectively halting electrical conduction.
However, this is where the nuances come into play.
Chen explains, "We have discovered that this vapor barrier is inherently leaky, dictated by the principles of physics. This means that while the soft gate of the BK channel can usually halt the flow of potassium ions, it is unable to do so completely—there is always a slight chance that ions will slip past. The soft gate is 'intrinsically open' even when the channel should be entirely closed."
Additionally, the researchers identified that the leakiness of this soft gate can be affected by various factors, including mutations that alter the physical properties of the BK channel itself.
These findings collectively pave the way for a deeper insight into the workings and potential malfunctions of BK channels and similar structures. The challenge lies in studying a vapor barrier, as it represents the absence of something expected. Yet, the inherent leaky nature of these channels offers a valuable opportunity for laboratory manipulation and may serve as a diagnostic tool for future investigations into the body’s electrical systems, as suggested by the scientists.
This important research received support from the National Institutes of Health.
