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Protein-protein interaction plays a key role in the regulation of biological processes. The human potassium (HERG) channel is encoded by the ether-a-go-go-related gene (herg), and its activity may be regulated by association with other cellular proteins. To identify cellular proteins that might play a role in the regulation of the HERG channel, we screened a human heart cDNA library with the N terminus of HERG using a yeast 2-hybrid system, and identified caveolin-1 as a potential HERG partner. The interaction between these 2 proteins was confirmed by coimmunoprecipitation assay, and their overlapping subcellular localization was demonstrated by fluorescence immunocytochemistry. The physiologic implication of the protein-protein interaction was studied in whole-cell patch-clamp electrophysiology experiments. A significant increase in HERG current amplitude and a faster deactivation of tail current were observed in HEK293/HERG cells in a membrane lipid rafts disruption model and caveolin-1 knocked down cells by RNA interference. Alternatively, when caveolin-1 was overexpressed, the HERG current amplitude was significantly reduced and the tail current was deactivated more slowly. Taken together, these data indicate that HERG channels interact with caveolin-1 and are negatively regulated by this interaction. The finding from this study clearly demonstrates the regulatory role of caveolin-1 on HERG channels, and may help to understand biochemical events leading to arrhythmogenesis in the long QT syndrome in cardiac patients. Key words: HERG, caveolin-1, lipid rafts, potassium channel, protein-protein interaction. Les interactions proteine-proteine jouent un role cle dans la regulation des processus biologiques. Le canal potassique humain HERG est code par le gene ether-a-go-go (herg) et son activite peut etre regulee par son association avec d'autres proteines cellulaires. Afin d'identifier les proteines cellulaires qui pourraient jouer un role dans la regulation du canal HERG, nous avons crible une banque d'ADNc de coeur humain a l'aide de l'extremite N-terminale de HERG dans un systeme de double-hybride de levure et nous avons identifie la caveoline-1 comme partenaire potentiel de HERG. L'interaction entre ces deux proteines a ete confirmee par un essai de co-immunoprecipitation et le chevauchement de leur localisation subcellulaire a ete demontre par immunocytochimie en fluorescence. L'implication physiologique de cette interaction proteine-proteine a ete etudiee par des experiences electrophysiologiques en patch-clamp. Une augmentation significative de l'amplitude du courant de HERG et une desactivation plus rapide du courant de queue ont ete observes chez les cellules HEK293/HERG dans un modele de desorganisation des radeaux lipidiques et apres extinction de la caveoline1 par interference d'ARN. A l'oppose, lorsque la caveoline-1 est surexprimee, l'amplitude du courant de HERG est significativement reduite et le courant de queue est desactive plus lentement. L'ensemble de ces resultats indique que les canaux HERG interagissent avec la caveoline-1 et qu'ils sont regules negativement par cette interaction. Cette etude demontre clairement le role regulateur de la caveoline-1 sur les canaux HERG et peut contribuer a comprendre les evenements biochimiques responsables du developpement de l'arythmie chez les patients cardiaques atteints du syndrome du QT long. Mots-cles : HERG, caveoline-1, radeaux lipidiques, canal potassique, interaction proteine-proteine. [Traduit par la Redaction], Introduction The human ether-a-go-go related gene (herg) is a human homolog of the Drosophila ether-a-go-go gene. The mutation of this gene in fruit flies would cause the shaking of legs [...]

Abstract: The objective of this study is to investigate the effects of preconditioning on the restoration and distribution of connexin 43 (Cx43) in ischemic myocardium in dogs. In this study, [...]

Abstract Background The levels and trends of cardiovascular risk factors vary greatly throughout China. We examine 10-year trends of cardiovascular risk factors (1983-1994) and the factors related to these trends among low-risk cohorts of workers and farmers in Guangzhou, China. Methods This is a cohort study of 3,131 workers and 3,493 farmers aged 25-64 years at baseline with 10 years of follow-up. We performed a longitudinal analysis to account for the aging of the cohorts and the repeated measures of the same individual. Results At baseline the prevalence of overweight (including obese) ranged from 1.0% to 11.8%, hypertension ranged from 3.8% to 10.5%, and mean serum total cholesterol (TC) ranged from 155.4 mg/dl to 187.2 mg/dl. Although prevalence of smoking declined, blood pressure levels and body mass index (BMI) increased significantly, and lipid profiles changed unfavorably during the 10-year follow-ups. The prevalence of hypertension increased from 5.0 percentage points (female farmers) to 12.3 percentage points (male farmers). Mean TC increased significantly (e.g., +22.8 mg/dl and +17.0 mg/dl in male and female farmers, respectively). In the longitudinal data analyses, increase in BMI was associated with increase in blood pressure levels and TC. Significant adverse trends of risk factors persisted after adjustment for aging, education, BMI, smoking, and alcohol intake. Conclusion Urgent action is needed to prevent and reverse the unhealthy trends occurring among these low risk Chinese workers and farmers.