Cardiac IKr channels minimally comprise hERG 1a and 1b subunits.
Previous studies suggest native cardiac IKr channels are composed of alpha subunits encoded solely by the 1a transcript of the ERG1 gene. Using isoform-specific ERG1 antibodies, we have new evidence that subunits encoded by an alternate transcript, ERG1b, are also expressed in rat, canine, and human heart. The ERG1a and -1b subunits associate in vivo where they localize to the T tubules of ventricular myocytes. These data indicate native ventricular IKr channels are heteromers containing two alpha subunit types, ERG1a and -1b. The hERG1b-specific exon thus represents a novel target to screen for mutations causing type 2 long QT syndrome. These findings also suggest phenotypic analyses of existing type 2 long QT syndrome mutations, especially those exclusive to the hERG1a amino terminus, should be carried out in systems expressing both subunits.
Jones
Eugenia M C
EM
Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Roti Roti
Elon C
EC
Wang
Jinling
J
Delfosse
Samantha A
SA
Robertson
Gail A
GA
D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005091:Exons; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008133:Long QT Syndrome / Q000378:metabolism; D008297:Male; D032342:Muscle Cells / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014162:Transfection
D027682:Cation Transport Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger