Targeting ryanodine receptors for anti-arrhythmic therapy

Antiarrhythmic drugs are a group of pharmaceuticals that suppress or prevent abnormal heart rhythms, which are often associated with substantial morbidity and mortality. Current antiarrhythmic drugs that typically target plasma membrane ion channels have limited clinical success and in some cases ha...

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Bibliographic Details
Published inActa pharmacologica Sinica Vol. 32; no. 6; pp. 749 - 757
Main Authors McCauley, Mark D, Wehrens, Xander H T
Format Journal Article
LanguageEnglish
Published United States Nature Publishing Group 01.06.2011
Subjects
Animals
Anti-Arrhythmia Agents - chemistry
Anti-Arrhythmia Agents - pharmacology
Anti-Arrhythmia Agents - therapeutic use
Arrhythmia
Arrhythmias, Cardiac - drug therapy
Arrhythmias, Cardiac - metabolism
Calcium
Calcium (reticular)
Calcium - metabolism
Cardiac muscle
Fibrillation
Heart
Heart diseases
Humans
Ion channels
Leak channels
Molecular modelling
Morbidity
Mortality
Pharmaceuticals
Plasma membranes
Review
Rhythms
Ryanodine Receptor Calcium Release Channel - genetics
Ryanodine Receptor Calcium Release Channel - metabolism
Ryanodine Receptor Calcium Release Channel - physiology
Ryanodine receptors
ryanodine受体
Sarcoplasmic reticulum
Sarcoplasmic Reticulum - drug effects
Sarcoplasmic Reticulum - metabolism
Tachycardia
儿茶酚胺
分子机制
心力衰竭
心脏疾病
抗心律失常
治疗
药物
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Summary:Antiarrhythmic drugs are a group of pharmaceuticals that suppress or prevent abnormal heart rhythms, which are often associated with substantial morbidity and mortality. Current antiarrhythmic drugs that typically target plasma membrane ion channels have limited clinical success and in some cases have been described as being pro-arrhythmic. However, recent studies suggest that pathological release of calcium （Ca2＋） from the sarcoplasmic reticulum via cardiac ryanodine receptors （RyR2） could represent a promising target for antiarrhythmic therapy. Diastolic SR Ca2＋ release has been linked to arrhythmogenesis in both the inherited arrhythmia syndrome ＇catecholaminergic polymorphic ventricular tachycardia＇ and acquired forms of heart disease （eg, atrial fibrillation, heart failure） Several classes of pharmaceuticals have been shown to reduce abnormal RyR2 activity and may confer protection against triggered arrhythmias through reduction of SR Ca2＋ leak. In this review, we will evaluate the current pharmacological methods for stabilizing RyR2 and suggest treatment modaiities based on current evidence of molecular mechanisms.
Bibliography:Antiarrhythmic drugs are a group of pharmaceuticals that suppress or prevent abnormal heart rhythms, which are often associated with substantial morbidity and mortality. Current antiarrhythmic drugs that typically target plasma membrane ion channels have limited clinical success and in some cases have been described as being pro-arrhythmic. However, recent studies suggest that pathological release of calcium （Ca2＋） from the sarcoplasmic reticulum via cardiac ryanodine receptors （RyR2） could represent a promising target for antiarrhythmic therapy. Diastolic SR Ca2＋ release has been linked to arrhythmogenesis in both the inherited arrhythmia syndrome ＇catecholaminergic polymorphic ventricular tachycardia＇ and acquired forms of heart disease （eg, atrial fibrillation, heart failure） Several classes of pharmaceuticals have been shown to reduce abnormal RyR2 activity and may confer protection against triggered arrhythmias through reduction of SR Ca2＋ leak. In this review, we will evaluate the current pharmacological methods for stabilizing RyR2 and suggest treatment modaiities based on current evidence of molecular mechanisms.
arrhythmias; atrial fibrillation; calcium; heart failure; ryanodine receptor; sarcoplasmic reticulum
31-1347/R
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ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2011.44