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In comparison to cation (K~+,Na~+,and Ca~(2+)) channels,much less is currentlyknown about the functional role of anion (Cl~-) channels in cardiovascular physiol-ogy and pathophysiology.Over the past 15 years,various types of Cl~- currentshave been recorded in cardiac cells from different species including humans.Allcardiac Cl~- channels described to date may be encoded by five different Cl~- chan-nel genes:the PKA- and PKC-activated cystic fibrosis tansmembrane conduc-tance regulator (CFTR),the volume-regulated CLC-2 and CIC-3,and the Ca~(2+)-activated CLCA or Bestrophin.Recent studies using multiple approaches toexamine the functional role of Cl~- channels in the context of health and diseasehave demonstrated that Cl~- channels might contribute to:1) arrhythmogenesis inmyocardial 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 approachesto 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 necessitateda new paradigm shift to the structural and functional assessment of integrated Cl~-channel multiprotein complexes in the heart,which could provide new insight intoour understanding of the underlying mechanisms responsible for heart diseaseand protection.
Much less is currentlyknown about the functional role of anion (Cl ~ -) channels in cardiovascular physiol -ogy and pathophysiology. Over the past (K ~ +, Na ~ +, and Ca ~ 15 years, various types of Cl ~ - currentshave been recorded in cardiac cells from different species including humans. Allcardiac Cl ~ - channels described to date may be encoded by five different Cl ~ - chan-nel genes: the PKA- and PKC-activated Cystic fibrosis tansmembrane conduc-tance regulator (CFTR), the volume-regulated CLC-2 and CIC-3, and the Ca ~ (2 +) - activated CLCA or Bestrophin.Recent studies using multiple approaches toexamine the functional role of Cl ~ channels in the context of health and diseasehave demonstrated that Cl ~ - channels may contribute to: 1) arrhythmogenesis in myocardial infarction; 2) cardiac ischemic preconditioning; and 3) the adaptive re-modeling of the heart during myocardial hypertrophy and heart failure. anion channels represent very attractive novel targets for the Rpeutic approachesto the treatment of heart diseases.Recent evidence suggests that Cl ~ --central channels, like cation channels, might function as a multiprotein complex or functional module.In the post-genome era, the emergence of functional proteomics has necessitateda new paradigm shift to the structural and functional assessment of integrated Cl ~ -channel multiprotein complexes in the heart, which could provide new insight intoour understanding of the underlying mechanisms responsible for heart disease and protection.