Functional role of anion channels in cardiac diseases¹

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 CIC-2 und CIC-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 mycocardial injury: 2)Cardiac ischemic preconditioning;: and 3) the adaptive re-modeling 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.