Interaction of the K Channel β Subunit,Hyperkinetic, with eag Family Members

Assembly of K channel α subunits of the Shaker ( Sh ) family occurs in a subfamily specific manner. It has been suggested that subfamily specificity also applies in the association of β subunits with Sh channels (Rhodes, K. J., Keilbaugh, S. A., Barrezueta, N. X., Lopez, K. L., and Trimmer, J. S. (1995) J. Neurosci. 15, 5360–5371; Sewing, S., Roeper, J. and Pongs, O. (1996) Neuron 16, 455–463; Yu, W., Xu, J., and Li, M. (1996) Neuron 16, 441–453). Here we show that the Drosophila β subunit homologue Hyperkinetic ( Hk ) associates with members of the ether à go-go ( eag ), as well as Sh , families. Anti-EAG antibody coprecipitates EAG and HK indicating a physical association between proteins. Heterologously expressed Hk dramatically increases the amplitudes of eag currents and also affects gating and modulation by progesterone. Through their ability to interact with a range of α subunits, the β subunits of voltage-gated K channels are likely to have a much broader impact on the signaling properties of neurons and muscle fibers than previously suggested.