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Volume 17, Number 21, Issue of November 1, 1997 pp. 8246-8258
Copyright ©1997 Society for Neuroscience

Association and Colocalization of the Kvbeta 1 and Kvbeta 2 beta -Subunits with Kv1 alpha -Subunits in Mammalian Brain K+ Channel Complexes

Received June 16, 1997; revised Aug. 13, 1997; accepted Aug. 18, 1997.

Kenneth J. Rhodes1, Brian W. Strassle1, Michael M. Monaghan1, Zewditu Bekele-Arcuri2, Maria F. Matos2, and James S. Trimmer2

1 Central Nervous System Disorders, Wyeth-Ayerst Research, Princeton, New Jersey 08543, and 2 Department of Biochemistry and Cell Biology and Institute for Cell and Developmental Biology, State University of New York, Stony Brook, New York 11794

The differential expression and association of cytoplasmic beta -subunits with pore-forming alpha -subunits may contribute significantly to the complexity and heterogeneity of voltage-gated K+ channels in excitable cells. Here we examined the association and colocalization of two mammalian beta -subunits, Kvbeta 1 and Kvbeta 2, with the K+ channel alpha -subunits Kv1.1, Kv1.2, Kv1.4, Kv1.6, and Kv2.1 in adult rat brain. Reciprocal coimmunoprecipitation experiments using subunit-specific antibodies indicated that Kvbeta 1 and Kvbeta 2 associate with all the Kv1 alpha -subunits examined, and with each other, but not with Kv2.1. A much larger portion of the total brain pool of Kv1-containing channel complexes was found associated with Kvbeta 2 than with Kvbeta 1. Single- and multiple-label immunohistochemical staining indicated that Kvbeta 1 codistributes extensively with Kv1.1 and Kv1.4 in cortical interneurons, in the hippocampal perforant path and mossy fiber pathways, and in the globus pallidus and substantia nigra. Kvbeta 2 codistributes extensively with Kv1.1 and Kv1.2 in all brain regions examined and was strikingly colocalized with these alpha -subunits in the juxtaparanodal region of nodes of Ranvier as well as in the axons and terminals of cerebellar basket cells. Taken together, these data provide a direct demonstration that Kvbeta 1 and Kvbeta 2 associate and colocalize with Kv1 alpha -subunits in native tissues and provide a biochemical and neuroanatomical basis for the differential contribution of Kv1 alpha - and beta -subunits to electrophysiologically diverse neuronal K+ currents.

Key words: ion channel; central nervous system; cerebellum; striatum; immunoprecipitation; immunohistochemistry; immunofluorescence; epilepsy




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