title: Functional role of anion channels in cardiac diseases.
abstract: In comparison to cation (K+, Na+, and Ca2+) channels, much less is currently known about the functional role of anion (Cl-) channels in cardiovascular physiology and pathophysiology. Over the past 15 years, various types of Cl- currents have been recorded in cardiac cells from different species including humans. All cardiac Cl- channels described to date may be encoded by five different Cl- channel genes: the PKA- and PKC-activated cystic fibrosis tansmembrane conductance regulator (CFTR), the volume-regulated ClC-2 and ClC-3, and the Ca2+-activated CLCA or Bestrophin. Recent studies using multiple approaches to examine the functional role of Cl- channels in the context of health and disease have demonstrated that Cl- channels might contribute to: 1) arrhythmogenesis in myocardial injury; 2) cardiac ischemic preconditioning; and 3) the adaptive remodeling of the heart during myocardial hypertrophy and heart failure. Therefore, anion channels represent very attractive novel targets for therapeutic approaches to the treatment of heart diseases. Recent evidence suggests that Cl- channels, like cation channels, might function as a multiprotein complex or functional module. In the post-genome era, the emergence of functional proteomics has necessitated a new paradigm shift to the structural and functional assessment of integrated Cl- channel multiprotein complexes in the heart, which could provide new insight into our understanding of the underlying mechanisms responsible for heart disease and protection.
authors.affiliation: Center of Biomedical Research Excellence, Department of Pharmacology, School of Medicine, University of Nevada, Reno, Nevada 89557-0270, USA. dduan@med.unr.edu
authors.forename: Da-yue
authors.initials: DY
authors.lastname: Duan
authors.forename: Luis L H
authors.initials: LL
authors.lastname: Liu
authors.forename: Nathan
authors.initials: N
authors.lastname: Bozeat
authors.forename: Z Maggie
authors.initials: ZM
authors.lastname: Huang
authors.forename: Sunny Y
authors.initials: SY
authors.lastname: Xiang
authors.forename: Guan-lei
authors.initials: GL
authors.lastname: Wang
authors.forename: Linda
authors.initials: L
authors.lastname: Ye
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Hume
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000503:physiopathology*; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D019194:Ischemic Preconditioning
chemical_list: C505032:CFTR protein, human; C492109:CLCA1 protein, human; D018118:Chloride Channels; C115376:ClC-3 channel; D019005:Cystic Fibrosis Transmembrane Conductance Regulator