Two patterns of ion channelopathy in the myocardium: perspectives for development of anti-arrhythmic agents.

Abstract

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.

• Authors: De-Zai Dai
• Journal: Current opinion in investigational drugs (London, England : 2000) (Curr Opin Investig Drugs) Vol. 6 Issue 3 Pg. 289-97 (Mar 2005) ISSN: 1472-4472 [Print] England
• PMID: 15816506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-Arrhythmia Agents
• Calcium Channels
• Ion Channels
• Muscle Proteins
• Ryanodine Receptor Calcium Release Channel
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• Tacrolimus Binding Proteins
• Calcium-Transporting ATPases

Topics

• Animals
• Anti-Arrhythmia Agents (chemistry, therapeutic use)
• Calcium Channels (drug effects, metabolism)
• Calcium-Transporting ATPases (metabolism)
• Cardiomegaly (drug therapy)
• Humans
• Ion Channels (drug effects, metabolism, physiopathology)
• Muscle Proteins (metabolism)
• Myocardium (metabolism, pathology)
• Ryanodine Receptor Calcium Release Channel (drug effects, metabolism)
• Sarcoplasmic Reticulum (drug effects, metabolism)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• Tacrolimus Binding Proteins (metabolism)