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Ryanodine receptor mutations in arrhythmia: The continuing mystery of channel dysfunction
Author(s) -
Thomas N. Lowri,
Maxwell Chloé,
Mukherjee Saptarshi,
Williams Alan J.
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.01.057
Subject(s) - ryanodine receptor , dysfunctional family , mutation , ryanodine receptor 2 , biology , function (biology) , sudden death , neuroscience , genetics , computational biology , bioinformatics , medicine , receptor , gene , psychiatry
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.