UCLA researchers have uncovered for the first time the molecular mechanism behind the biological sensor known as the “gating ring” which is responsible for the flow of potassium ions through the cell’s wall or membrane.
The findings, published in the June 10 issue of the Journal of Biological Chemistry and featured as a “Paper of the Week,” could lead to the development of specific therapies against diseases such as hypertension and genetic epilepsy.
When calcium ions bind the gating ring — which constitutes the intracellular part of an ionic channel known as the BK channel — the cell responds by allowing the flow of potassium ions across the cell membrane.
The UCLA researchers were able to identify for the first time how the gating ring is activated and how it rearranges itself to open the gateway that the ions flow through. Using state-of-the-art electrophysiological, biochemical and spectroscopic techniques in the laboratory, the team demonstrated that when calcium ions bind to the gating ring, its structure changes — that is, it converts the chemical energy of the calcium binding into mechanical work that facilitates the opening of the BK channel.
“We were able to resolve the biophysical changes occurring in the sensor, under conditions resembling those present inside a living cell, so we believe that these transformations reflect the molecular events occurring when BK channels operate in the body,” said research team leader Riccardo Olcese, an associate professor in the department of anesthesiology’s division of molecular medicine and a member of both the Cardiovascular Research Laboratory and Brain Research Institute at the David Geffen School of Medicine at UCLA.
“This is an exciting field of study and we hope that these findings will lead to a greater understanding of how this complex biological sensor operates,” said study author Anoosh D. Javaherian, a research associate in the department of anesthesiology’s division of molecular medicine division at the Geffen School of Medicine.
Javaherian added that only last year were the structures involved in the BK sensor even identified. This is the first study to demonstrate its function.
Since the BK channel and its sensor are involved in so many aspects of normal physiological function, researchers believe that it is likely the process could be implicated in many aspects of disease as well.
Tags: molecular biology