Ryanodine receptor mutations in arrhythmia: The continuing mystery of channel dysfunction.
Mutations in RyR2 are causative of an inherited disorder which often results in sudden cardiac death. Dysfunctional channel behaviour has been the subject of many investigations varying from single channel analysis through to complex animal models. This review discusses recent advances in the field, describes the controversy surrounding the exact consequences of RyR2 mutation and how the disparate data may be reconciled. This heterogeneity of function with respect to the effects of polymorphisms, phosphorylation, cytosolic and luminal Ca(2+) as well as inter-domain interactions may have important implications for the recent pharmaceutical therapies which have been put forward. We surmise that a comprehensive characterisation of mutations on a case-by-case basis may be beneficial for the development of specifically targeted therapies.
Department of Cardiology, Wales Heart Research Institute, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. ThomasNL1@cardiff.ac.uk
N Lowri
NL
Thomas
Chloé
C
Maxwell
Saptarshi
S
Mukherjee
Alan J
AJ
Williams
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D011110:Polymorphism, Genetic; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017180:Tachycardia, Ventricular / Q000188:drug therapy
D019837:Ryanodine Receptor Calcium Release Channel