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Volume 16, Number 16, Issue of August 15, 1996 pp. 4846-4860
Copyright ©1996 Society for Neuroscience

Voltage-Gated K+ Channel beta  Subunits: Expression and Distribution of Kvbeta 1 and Kvbeta 2 in Adult Rat Brain

Received Jan. 18, 1996; revised May 9, 1996; accepted May 21, 1996.

Kenneth J. Rhodes1, Michael M. Monaghan1, Nestor X. Barrezueta1, Stanley Nawoschik1, Zewditu Bekele-Arcuri2, Maria F. Matos2, Kensuke Nakahira2, Lee E. Schechter1, and James S. Trimmer2

1 CNS 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

Recent cloning of K+ channel beta  subunits revealed that these cytoplasmic polypeptides can dramatically alter the kinetics of current inactivation and promote efficient glycosylation and surface expression of the channel-forming alpha  subunits. Here, we examined the expression, distribution, and association of two of these beta  subunits, Kvbeta 1 and Kvbeta 2, in adult rat brain. In situ hybridization using cRNA probes revealed that these beta -subunit genes are heterogeneously expressed, with high densities of Kvbeta 1 mRNA in the striatum, CA1 subfield of the hippocampus, and cerebellar Purkinje cells, and high densities of Kvbeta 2 mRNA in the cerebral cortex, cerebellum, and brainstem. Immunohistochemical staining using subunit-specific monoclonal and affinity-purified polyclonal antibodies revealed that the Kvbeta 1 and Kvbeta 2 polypeptides frequently co-localize and are concentrated in neuronal perikarya, dendrites, and terminal fields, and in the juxtaparanodal region of myelinated axons. Immunoblot and reciprocal co-immunoprecipitation analyses indicated that Kvbeta 2 is the major beta  subunit present in rat brain membranes, and that most K+ channel complexes containing Kvbeta 1 also contain Kvbeta 2. Taken together, these data suggest that Kvbeta 2 is a component of almost all K+ channel complexes containing Kv1 alpha  subunits, and that individual channels may contain two or more biochemically and functionally distinct beta -subunit polypeptides.

Key words: ion channel; central nervous system; auxiliary subunit; striatum; immunoprecipitation; immunohistochemistry




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