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Ion channelopathy and hyperphosphorylation contributing to cardiac arrhythmias Dai DZ; Yu FActa Pharmacol Sin 2005[Aug]; 26 (8): 918-25The occurrence of cardiac arrhythmias is related to the abnormality of ion channels not only in sarcolemma but also in the sarcoplasmic reticulum, which regulates the process of calcium release and up-take intracellularly. Patterns of ion channelopathy in the sarcolemma can be divided into single channel disorder from gene mutations and multiple channels disorder in a diseased hypertrophied heart. Abnormal RyR2, FKBP12.6, SERCA2a, and PLB are also involved in the initiation of cardiac arrhythmias. Maladjustment by hyperphosphorylation on the ion channels in the sarcolemma and RyR2-FKBP12.6 and SERCA2a-PLB is discussed. Hyperphosphorylation, which is the main abnormality upstream to ion channels, can be targeted for suppressing the deterioration of ion channelopathy in terms of new drug discovery in the treatment and prevention of malignant cardiac arrhythmias.|Animals[MESH]|Anti-Arrhythmia Agents/therapeutic use[MESH]|Arrhythmias, Cardiac/drug therapy/*metabolism/physiopathology[MESH]|Calcium-Transporting ATPases/metabolism[MESH]|Humans[MESH]|Ion Channels/antagonists & inhibitors/genetics/*metabolism[MESH]|Mutation[MESH]|Phosphorylation[MESH]|Ryanodine Receptor Calcium Release Channel/metabolism[MESH]|Sarcoplasmic Reticulum Calcium-Transporting ATPases[MESH]|Sarcoplasmic Reticulum/*metabolism[MESH] |
