The ryanodine receptor in cardiac physiology and disease

Adv Pharmacol. 2010:59:1-30. doi: 10.1016/S1054-3589(10)59001-X.

Abstract

According to the American Heart Association it is estimated that the United States will spend close to $39 billion in 2010 to treat over five million Americans suffering from heart failure. Patients with heart failure suffer from dyspnea and decreased exercised tolerance and are at increased risk for fatal ventricular arrhythmias. Food and Drug Administration -approved pharmacologic therapies for heart failure include diuretics, inhibitors of the renin-angiotensin system, and β-adrenergic receptor antagonists. Over the past 20 years advances in the field of ryanodine receptor (RyR2)/calcium release channel research have greatly advanced our understanding of cardiac physiology and the pathogenesis of heart failure and arrhythmias. Here we review the key observations, controversies, and discoveries that have led to the development of novel compounds targeting the RyR2/calcium release channel for treating heart failure and for preventing lethal arrhythmias.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Atrial Fibrillation / metabolism*
  • Atrial Fibrillation / physiopathology
  • Atrial Fibrillation / therapy
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cardiovascular Agents / chemistry
  • Cardiovascular Agents / metabolism
  • Cardiovascular Agents / therapeutic use
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Drug Design
  • Heart Conduction System* / physiology
  • Heart Conduction System* / physiopathology
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Heart Failure / therapy
  • Humans
  • Infant, Newborn
  • Myocardial Contraction* / physiology
  • Phosphorylation
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Adrenergic, beta / physiology
  • Ryanodine Receptor Calcium Release Channel / chemistry
  • Ryanodine Receptor Calcium Release Channel / drug effects
  • Ryanodine Receptor Calcium Release Channel / physiology*
  • Sudden Infant Death / genetics
  • Sudden Infant Death / prevention & control
  • Tachycardia, Ventricular / metabolism*
  • Tachycardia, Ventricular / physiopathology
  • Tachycardia, Ventricular / therapy
  • Tacrolimus Binding Proteins / metabolism

Substances

  • Cardiovascular Agents
  • Receptors, Adrenergic, beta
  • Ryanodine Receptor Calcium Release Channel
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Tacrolimus Binding Proteins