Subunit composition determines Kv1 potassium channel surface expression

Shaker-related or Kv1 voltage-gated K+ channels play critical roles in regu lating the excitability of mammalian neurons. Native Kv1 channel complexes are octamers of four integral membrane alpha subunits and four cytoplasmic beta subunits, such that a tremendous diversity of channel complexes can be assembled from the array of alpha and beta subunits expressed in the brain . However, biochemical and immunohistochemical studies have demonstrated th at only certain complexes predominate in the mammalian brain, suggesting th at regulatory mechanisms exist that ensure plasma membrane targeting of onl y physiologically appropriate channel complexes. Here we show that Kv1 chan nels assembled as homo- or heterotetrameric complexes had distinct surface expression characteristics in both transfected mammalian cells and hippocam pal neurons. Homotetrameric Kv1.1 channels were localized to endoplasmic re ticulum, Kv1.4 channels to the cell surface, and Kv1.2 channels to both end oplasmic reticulum and the cell surface. Heteromeric assembly with Kv1.4 re sulted in dose-dependent increases in cell surface expression of coassemble d Kv1.1 and Kv1.2, while coassembly with Kv1.1 had a dominant-negative effe ct on Kv1.2 and Kv1.4 surface expression. Coassembly with Kv beta subunits promoted cell surface expression of each Kv1 heteromeric complex. These dat a suggest that subunit composition and stoichiometry determine surface expr ession characteristics of Kv1 channels in excitable cells.