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J. Biol. Chem., Vol. 282, Issue 35, 25548-25559, August 31, 2007

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Heteromeric Assembly of Acid-sensitive Ion Channel and Epithelial Sodium Channel Subunits^*

Robert H. Meltzer, Niren Kapoor, Yawar J. Qadri, Susan J. Anderson, Catherine M. Fuller, and Dale J. Benos¹

From the Departments of Physiology and Biophysics and Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294

Amiloride-sensitive ion channels are formed from homo- or heteromeric combinations of subunits from the epithelial Na⁺ channel (ENaC)/degenerin superfamily, which also includes the acid-sensitive ion channel (ASIC) family. These channel subunits share sequence homology and topology. In this study, we have demonstrated, using confocal fluorescence resonance energy transfer microscopy and co-immunoprecipitation, that ASIC and ENaC subunits are capable of forming cross-clade intermolecular interactions. We have also shown that combinations of ASIC1 with ENaC subunits exhibit novel electrophysiological characteristics compared with ASIC1 alone. The results of this study suggest that heteromeric complexes of ASIC and ENaC subunits may underlie the diversity of amiloride-sensitive cation conductances observed in a wide variety of tissues and cell types where co-expression of ASIC and ENaC subunits has been observed.

Received for publication, May 9, 2007 , and in revised form, June 27, 2007.

^* This work was supported by National Institutes of Health Grants CA101957, DK37206, and 5T32 DK 07545. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

¹ To whom correspondence should be addressed. Tel.: 205-934-6220; Fax: 205-934-2377; E-mail: benos{at}physiology.uab.edu.

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