In 2001, Italian researchers identified the culprit behind catecholaminergic polymorphic ventricular tachycardia: mutations in the cardiac ryanodine receptor (Circulation 2001; 103:196-200). The receptor serves as a channel that releases calcium ions needed for cardiac muscle contractions.
Thirteen years later, cardiologists can now watch this disorder in action in an animation that was unveiled Jan. 17 at the annual meeting of the American Association for the Advancement of Science in Boston. Filip Van Petegem, PhD, of the Life Sciences Institute at the University of British Columbia in Vancouver, presented a 3D animated model that illustrates how genetic mutations in the ryanodine receptor destabilize the structure, creating a “leaky” channel. Related findings by Petegem and colleagues were published Feb. 19 in Nature Communications.
“This detailed three-dimensional structure is going to be very useful in finding strategies to help stabilize this structure,” Petegem told Cardiovascular Business. Given the large number of genetic mutations, gene therapy is a not practical solution, he said, but a small molecule pharmaceutical might be developed that stabilizes the protein.
“One hallmark of this disease is that it is triggered by stress,” Petegem said. “The mutation by itself does not cause the arrhythmia; it is the combination of the mutation with stress.” His research group next wants to study how stress modulates this protein.