Regulation of HERG (KCNH2) potassium channel surface expression by diacylglycerol.
The HERG (KCNH2) channel is a voltage-sensitive potassium channel mainly expressed in cardiac tissue, but has also been identified in other tissues like neuronal and smooth muscle tissue, and in various tumours and tumour cell lines. The function of HERG has been extensively studied, but it is still not clear what mechanisms regulate the surface expression of the channel. In the present report, using human embryonic kidney cells stably expressing HERG, we show that diacylglycerol potently inhibits the HERG current. This is mediated by a protein kinase C-evoked endocytosis of the channel protein, and is dependent on the dynein-dynamin complex. The HERG protein was found to be located only in early endosomes and not lysosomes. Thus, diacylglycerol is an important lipid participating in the regulation of HERG surface expression and function.
Ramström
Cia
C
Department of Biology, Abo Akademi University, 20520, Turku, Finland.
Chapman
Hugh
H
Viitanen
Tero
T
Afrasiabi
Emad
E
Fox
Heli
H
Kivelä
Johanna
J
Soini
Sanna
S
Korhonen
Laura
L
Lindholm
Dan
D
Pasternack
Michael
M
Törnquist
Kid
K
D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology*; D034281:Dynamins / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism; D000072237:ERG1 Potassium Channel; D055724:Electrophysiological Phenomena / Q000187:drug effects; D004705:Endocytosis; D011992:Endosomes / Q000201:enzymology; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D011493:Protein Kinase C / Q000378:metabolism
D004075:Diglycerides; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D011493:Protein Kinase C; D004398:Dyneins; D034281:Dynamins