HETEROMULTIMERIC K+ CHANNELS IN TERMINAL AND JUXTAPARANODAL REGIONS OF NEURONS

VOLTAGE-GATED potassium (K+) channels display a wide variety of conductances and gating properties in vivo1-3. This diversity can be attributed not only to the presence of many K+-channel gene products, but also to the possibility that different K+-channel subunits co-assemble to form heteromultimeric channels in vivo. When expressed in Xenopus oocytes or transfected cells, K+-channel polypeptides assemble to form tetramers4. Certain combinations of Shaker-like subunits have been shown to co-assemble, forming heteromultimeric channels with distinct properties5-7. It is not known, however, whether K+-channel polypeptides form heteromultimeric channels in vivo. Here we describe the co-localization of two Shaker-like voltage-gated K+-channel proteins, mKv1.1 and mKv1.2, in the juxtaparanodal regions of nodes of Ranvier in myelinated axons, and in terminal fields of basket cells in mouse cerebellum. We also show that mKv1.1 and mKv1.2 can be co-immunoprecipitated with specific antibodies that recognize only one of them. These data indicate that the two polypeptides occur in subcellular regions where rapid membrane repolarization may be important and that they form heteromultimeric channels in vivo.