The regulation of the cardiac potassium channel (HERG) by caveolin-1

• Published in: Biochemistry and cell biology Vol. 86; no. 5; pp. 405 - 415
• Main Authors: Lin, Jijin, Lin, Shuguang, Choy, Patrick C, Shen, Xiuzhang, Deng, Chunyu, Kuang, Sujuan, Wu, Jun, Xu, Wencan
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.10.2008; Canadian Science Publishing NRC Research Press
• Subjects: Animals; Biochemistry; canal potassique; Caveolin 1 - genetics; Caveolin 1 - metabolism; caveolin-1; cavéoline-1; Cell Line; Cells; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels - genetics; Ether-A-Go-Go Potassium Channels - metabolism; Fluorescence; Genes; Heart; Heart - physiology; HERG; Humans; interaction protéine-protéine; lipid rafts; Long QT Syndrome - metabolism; Membrane Microdomains; Patch-Clamp Techniques; Potassium; potassium channel; protein-protein interaction; Proteins; radeaux lipidiques; Rats; Rats, Wistar; RNA Interference; Two-Hybrid System Techniques
• ISSN: 0829-8211; 1208-6002
• DOI: 10.1139/O08-118

Protein-protein interaction plays a key role in the regulation of biological processes. The human potassium (HERG) channel is encoded by the ether-à-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.