Association and Colocalization of the Kv (cid:98) 1 and Kv (cid:98) 2 (cid:98) -Subunits with Kv1 (cid:97) -Subunits in Mammalian Brain K (cid:49) Channel Complexes

The differential expression and association of cytoplasmic (cid:98) subunits with pore-forming (cid:97) -subunits may contribute signifi-cantly to the complexity and heterogeneity of voltage-gated K (cid:49) channels in excitable cells. Here we examined the association and colocalization of two mammalian (cid:98) -subunits, Kv (cid:98) 1 and Kv (cid:98) 2, with the K (cid:49) channel (cid:97) -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 Kv (cid:98) 1 and Kv (cid:98) 2 associate with all the Kv1 (cid:97) -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 Kv (cid:98) 2 than with Kv (cid:98) 1. Single- and multiple-label immunohistochemical staining indicated that Kv (cid:98) 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. Kv (cid:98) 2 codistributes extensively with Kv1.1 and Kv1.2 in all brain regions examined and was strikingly colocalized with these (cid:97) -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 Kv (cid:98) 1 and Kv (cid:98) 2 associate and colocalize with Kv1 (cid:97) subunits in native tissues and provide a biochemical and neuroanatomical basis for the differential contribution of Kv1 (cid:97) - and (cid:98) -subunits to electrophysiologically diverse neuronal K (cid:49) currents.

[1]  D. Papazian,et al.  Potassium Channel α and β Subunits Assemble in the Endoplasmic Reticulum* , 1997, The Journal of Biological Chemistry.

[2]  J. Trimmer,et al.  Generation and Characterization of Subtype-specific Monoclonal Antibodies to K+ Channel α- and β-subunit Polypeptides , 1996, Neuropharmacology.

[3]  K. Rhodes,et al.  Identification of a cytoplasmic domain important in the polarized expression and clustering of the Kv2.1 K+ channel , 1996, The Journal of cell biology.

[4]  M. Lazdunski,et al.  A New K+ Channel β Subunit to Specifically Enhance Kv2.2 (CDRK) Expression* , 1996, The Journal of Biological Chemistry.

[5]  M. Sheng,et al.  Ion channel associated proteins , 1996, Current Opinion in Neurobiology.

[6]  O. Pongs,et al.  Functional characterization of Kv channel beta‐subunits from rat brain. , 1996, The Journal of physiology.

[7]  K. Rhodes,et al.  βSubunits Promote K+ Channel Surface Expression through Effects Early in Biosynthesis , 1996, Neuron.

[8]  J. Priestley,et al.  Ultrastructural Localization of a Voltage‐gated K+ Channel a Subunit (Kv1.2) in the Rat Cerebellum , 1996, The European journal of neuroscience.

[9]  K. Rhodes,et al.  Selective Interaction of Voltage-gated K Channel -Subunits with -Subunits (*) , 1996, The Journal of Biological Chemistry.

[10]  O. Pongs,et al.  Kvβ1 Subunit Binding Specific for Shaker-Related Potassium Channel α Subunits , 1996, Neuron.

[11]  O. Pongs,et al.  Molecular and functional characterization of a rat brain Kv β3 potassium channel subunit , 1995, FEBS letters.

[12]  V. Uebele,et al.  A Novel K+ Channel β-Subunit (hKvβ1.3) Is Produced via Alternative mRNA Splicing (*) , 1995, The Journal of Biological Chemistry.

[13]  Y. Jan,et al.  Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases , 1995, Nature.

[14]  O. Pongs,et al.  Immunohistochemical Localization of Five Members of the KV1 Channel Subunits: Contrasting Subcellular Locations and Neuron‐specific Co‐localizations in Rat Brain , 1995, The European journal of neuroscience.

[15]  B. Rudy,et al.  Alternative splicing of the human Shaker K+ channel β1 gene and functional expression of the β2 gene product , 1995 .

[16]  H. Shear,et al.  Characterization of a voltage-gated K+ channel beta subunit expressed in human heart. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  O. Pongs.  Regulation of the activity of voltage-gated potassium channels by β subunits , 1995 .

[18]  H. Strauss,et al.  A Novel β Subunit Increases Rate of Inactivation of Specific Voltage-gated Potassium Channel α Subunits (*) , 1995, The Journal of Biological Chemistry.

[19]  B. Wible,et al.  Molecular cloning and functional expression of a novel potassium channel β‐subunit from human atrium , 1995 .

[20]  J. Trimmer,et al.  Properties of Kv2.1 K+ channels expressed in transfected mammalian cells. , 1994, The Journal of biological chemistry.

[21]  P. Schwartzkroin,et al.  Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  O. Pongs,et al.  Inactivation properties of voltage-gated K+ channels altered by presence of β-subunit , 1994, Nature.

[23]  Y. Jan,et al.  Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  O. Pongs,et al.  Antibodies specific for distinct Kv subunits unveil a heterooligomeric basis for subtypes of alpha-dendrotoxin-sensitive K+ channels in bovine brain. , 1994, Biochemistry.

[25]  J. Dolly,et al.  Prominent location of a K+ channel containing the α subunit KV 1.2 in the basket cell nerve terminals of rat cerebellum , 1993, Neuroscience.

[26]  Yuh Nung Jan,et al.  Presynaptic A-current based on heteromultimeric K+ channels detected in vivo , 1993, Nature.

[27]  P. Schwartzkroin,et al.  Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons , 1993, Nature.

[28]  J. Dolly,et al.  Oligomeric properties of alpha-dendrotoxin-sensitive potassium ion channels purified from bovine brain. , 1992, Biochemistry.

[29]  B. Sakmann,et al.  Heteromultimeric channels formed by rat brain potassium-channel proteins , 1990, Nature.

[30]  A. Feltz,et al.  Dendrotoxin-sensitive K+ channels in dorsal root ganglion cells , 1988, Neuroscience Letters.

[31]  Y. Jan,et al.  Cloned potassium channels from eukaryotes and prokaryotes. , 1997, Annual review of neuroscience.

[32]  A. Harvey,et al.  Recent studies on dendrotoxins and potassium ion channels. , 1997, General pharmacology.

[33]  W Vogel,et al.  Single voltage‐dependent potassium channels in rat peripheral nerve membrane. , 1993, The Journal of physiology.

[34]  Douglas L. Rosene,et al.  The Hippocampal Formation of the Primate Brain , 1987 .

[35]  J. Sportsman,et al.  Improved technique utilizing nonfat dry milk for analysis of proteins and nucleic acids transferred to nitrocellulose , 1984 .

[36]  R. Keynes.  The ionic channels in excitable membranes. , 1975, Ciba Foundation symposium.

[37]  Jacob V. Maizel,et al.  Polyacrylamide Gel Electrophoresis of Viral Proteins , 1971 .

[38]  J. N. Keen,et al.  Primary structure of a 13 subunit of a-dendrotoxin-sensitive K+ channels from bovine brain , 2022 .