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Papers In Press, published online ahead of print August 10, 2004
J. Biol. Chem, 10.1074/jbc.M408344200
Submitted on July 23, 2004
Revised on August 10, 2004
Accepted on August 10, 2004

Cardiac IKr channels minimally comprise hERG1a and 1b subunits

Eugenia M. C. Jones, Elon C. Roti Roti, Jinling Wang, Samantha A. Delfosse, and Gail A. Robertson

Department of Physiology, University of Wisconsin-Madison, Madison, WI 53706

Corresponding Author: robertson{at}physiology.wisc.edu

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 (LQTS-2). These findings also suggest phenotypic analyses of existing LQTS-2 mutations, especially those exclusive to the hERG1a amino terminus, should be carried out in systems expressing both subunits.


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