title: Phenomics of cardiac chloride channels.
abstract: Forward genetic studies have identified several chloride (Cl-) channel genes, including CFTR, ClC-2, ClC-3, CLCA, Bestrophin, and Ano1, in the heart. Recent reverse genetic studies using gene targeting and transgenic techniques to delineate the functional role of cardiac Cl- channels have shown that Cl- channels may contribute to cardiac arrhythmogenesis, myocardial hypertrophy and heart failure, and cardioprotection against ischemia reperfusion. The study of physiological or pathophysiological phenotypes of cardiac Cl- channels, however, is complicated by the compensatory changes in the animals in response to the targeted genetic manipulation. Alternatively, tissue-specific conditional or inducible knockout or knockin animal models may be more valuable in the phenotypic studies of specific Cl- channels by limiting the effect of compensation on the phenotype. The integrated function of Cl- channels may involve multiprotein complexes of the Cl- channel subproteome. Similar phenotypes can be attained from alternative protein pathways within cellular networks, which are influenced by genetic and environmental factors. The phenomics approach, which characterizes phenotypes as a whole phenome and systematically studies the molecular changes that give rise to particular phenotypes achieved by modifying the genotype under the scope of genome/proteome/phenome, may provide more complete understanding of the integrated function of each cardiac Cl- channel in the context of health and disease.
authors.affiliation: The Laboratory of Cardiovascular Phenomics, Department of Pharmacology, University of Nevada, School of Medicine, Reno, Nevada, USA. dduan@medicine.nevada.edu
authors.forename: Dayue Darrel
authors.initials: DD
authors.lastname: Duan
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006801:Humans; D010641:Phenotype
chemical_list: D018118:Chloride Channels