Montserrat Samso, PhD, of BWH, and colleagues have mapped the structure of the ryanodine receptor (RyR1), a calcium channel involved in the final signal transduction step of muscle contraction. Mutations of RyR1 can lead to central core disease and malignant hyperthermia, and mapping the structure is a necessary first step before beginning to understand its function. These findings appear in the April 2009 issue of PLoS Biology.  
 
Due to its large size, structural determination of RyR1 using classical structural techniques such as NMR or x-ray crystallography was impossible, but this protein proved to be very amenable to be studied by cryo-electron microscopy and single-particle image processing. Using this method Dr. Samso determined the closed state of the channel in 2005, but to determine the open state, Dr. Samso enlisted the help of two scientists from the University of California, Davis. The channel is typically only in the open state for few milliseconds, but using the chemical compound PCB 95, the scientists were able to fix the channel open for an extended period, allowing for a detailed image to be created of the channel in its open state.
 
With complete images of the structure of RyR1 in both open and closed states, mapping the function is the next step in better understanding the channel. Investigators also hope to use this information in the study of RyR2, the cardiac form of this channel. Mutations in this channel can result in sudden cardiac death.

The American Heart Association, the BWH Biomedical Research Institute, and the National Institutes of Health funded this research.