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J. Biol. Chem., Vol. 279, Issue 43, 44690-44694, October 22, 2004

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Cardiac I_Kr Channels Minimally Comprise hERG 1a and 1b Subunits^*

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

From the Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706

Previous studies suggest native cardiac I_Kr 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 I_Kr channels are heteromers containing two 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.

Received for publication, July 23, 2004

^* This research was supported by National Institutes of Health Grant R01 HL68868 (to G. A. R.) and Training Grant T32 HL07936 (to E. C. R. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 608-265-3339; Fax: 608-265-5512; E-mail: Robertson{at}physiology.wisc.edu.

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