Altered RyR2 regulation by the calmodulin F90L mutation associated with idiopathic ventricular fibrillation and early sudden cardiac death

作者：Nomikos Michail^*; Thanassoulas Angelos; Beck Konrad; Vassilakopoulou Vyronia; Hu Handan; Calver Brian L; Theodoridou Maria; Kashir Junaid; Blayney Lynda; Livaniou Evangelia; Rizkallah Pierre; Nounesis George; Lai F Anthony

来源：FEBS LETTERS, 2014, 588(17): 2898-2902.

DOI：10.1016/j.febslet.2014.07.007

• Calmodulin
• Calcium
• Ryanodine receptor
• RyR2 calcium release channel
• Idiopathic ventricular fibrillation
• Sudden cardiac death

Calmodulin (CaM) association with the cardiac muscle ryanodine receptor (RyR2) regulates excitation-contraction coupling. Defective CaM-RyR2 interaction is associated with heart failure. A novel CaM mutation (CaMF90L) was recently identified in a family with idiopathic ventricular fibrillation (IVF) and early onset sudden cardiac death. We report the first biochemical characterization of CaMF90L. F90L confers a deleterious effect on protein stability. Ca2+-binding studies reveal reduced Ca2+-binding affinity and a loss of co-operativity. Moreover, CaMF90L displays reduced RyR2 interaction and defective modulation of [H-3] ryanodine binding. Hence, dysregulation of RyR2-mediated Ca2+ release via aberrant CaMF90L-RyR2 interaction is a potential mechanism that underlies familial IVF. %26lt;br%26gt;Structured summary of prote

• 出版日期2014-8-25