Two patterns of ion channelopathy in the myocardium: perspectives for development of anti-arrhythmic agents.
Cardiac arrhythmia remains a significant problem, due to the high morbidity and mortality associated with cardiovascular diseases with prominent cardiac remodeling. There is still a lack of effective drugs with which to combat this life-threatening disorder. The abnormal electrophysiological properties of the heart can be explained in terms of ion channels and channelopathy and, in recent years, advances have been made in understanding these properties. There are two patterns of ion channelopathies in the diseased heart: Single insufficiency disorder, which is attributed to mutations in genes, and a multiple derangement of channels. Malignant arrhythmias in a diseased heart usually occur when ventricular hypertrophy is evident, and when they are associated with abnormal repolarization. Abnormalities in the ryanodine receptor-calcium release channel complex (RyR)2, FK-506 binding protein (FKBP 12.6), cardiac sarcoplasmic reticulum calcium ATPase (SERCA2a) and phospholamban (PLB) are involved in the initiation of cardiac arrhythmias, and can be identified as targets for therapeutic interventions.
Dai
De-Zai
DZ
China Pharmaceutical University, Research Division of Pharmacology, Zhongyang Road, 24 Tongjia Lane, Nanjing 210009, China. dezaidai@vip.sina.com
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000627:therapeutic use*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006332:Cardiomegaly / Q000188:drug therapy; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects* / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D022021:Tacrolimus Binding Proteins / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D007473:Ion Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D022021:Tacrolimus Binding Proteins; D000252:Calcium-Transporting ATPases