Does dantrolene rescue aberrant N-terminus intersubunit interactions in mutant pro-arrhythmic cardiac ryanodine receptors?
The N-terminus domain constitutes an important structural determinant for the functional oligomerization of RyR2. Our findings are consistent with defective N-terminus self-association as a molecular mechanism underlying RyR2 channel deregulation in inherited arrhythmogenic cardiac disease. Significantly, the therapeutic action of dantrolene may occur via the restoration of normal RyR2 N-terminal intersubunit interactions.
Bacterial infection is associated with failure to control UGIB and early mortality in cirrhotic patients, but does not seem to affect the outcome of patients who overcome the bleeding episode.