Heteromultimeric interactions among K+ channel subunits from Shaker and eag families in Xenopus oocytes

Heteromultimeric interactions of K+ channel subunits across different families have been thought to contribute to the functional diversity of ionic currents, as suggested by previous genetic evidence. We present here direct demonstration in Xenopus oocytes that subunits from distinct eag and Shaker families functionally interact, most likely as heteromultimeric channels. Coexpression with eag accelerates the inactivation and slows the recovery from inactivation of the transient Shaker current. Site-directed mutagenesis indicates that the eag carboxyl terminus is crucial for this interaction, exerting effects preferentially on N-type inactivation. Many members of the eag and Shaker families have now been identified and their human homologs implicated in cardiac and neurological disorders. Studies on channel subunit interactions may prove important in understanding the disease pattern and the complex functions of the brain.