title: A functional spliced-variant of beta 2 subunit of Kv1 channels in C6 glioma cells and reactive astrocytes from rat lesioned cerebellum.
abstract: Voltage-gated K(+) channels (Kv1) are important in glia, being required for cell proliferation. Herein, reactive astrocytes from a rat cerebellar lesion were shown to contain Kv1.1, -1.2, -1.3, -1.4, and -1.6 alpha plus beta1.1 subunits, as well as an unusual beta2.1 constituent; the latter was also found in a glioblastoma C6 cell line, together with Kv1.1, -1.3, and -1.6 and beta1.1 subunits. Reverse transcriptase-polymerase chain reaction revealed a novel product of the beta2 gene in C6 cells and reactive astrocytes, but not in cultured astrocytes or rat normal brain. Its cloning identified a variant, Kvbeta2.1A, alternatively spliced between I24 and Y39. Despite this 14 residue deletion, Kvbeta2.1A assembled cotranslationally with Kv1.1 or -1.2 and, when coexpressed with Kv1. 4 in oocytes, increased the inactivation rate of this K(+) current. Whereas the full-length beta2.1 gave a large increase in the amplitude of the Kv1.1 current in oocytes, the effect of beta2.1A varied from a modest elevation of the current to a slight suppression in some cases. In summary, this is the first report of the existence of an alternatively spliced product of the Kvbeta2.1 gene in C6 cells and reactive astrocytes, and supports the involvement of its core region (residues 39 onward) in assembly with alpha subunits while excluding a contribution of the adjacent 14 residues to accelerating the inactivation of Kv1.4.
authors.affiliation: Department of Biochemistry, Imperial College of Science, Technology & Medicine, London, U.K.
authors.forename: S
authors.initials: S
authors.lastname: Akhtar
authors.forename: P
authors.initials: P
authors.lastname: McIntosh
authors.forename: A
authors.initials: A
authors.lastname: Bryan-Sisneros
authors.forename: L
authors.initials: L
authors.lastname: Barratt
authors.forename: B
authors.initials: B
authors.lastname: Robertson
authors.forename: J O
authors.initials: JO
authors.lastname: Dolly
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D003001:Cloning, Molecular; D005910:Glioma / Q000378:metabolism*; D051662:Kv1.1 Potassium Channel; D051663:Kv1.2 Potassium Channel; D008564:Membrane Potentials / Q000235:genetics; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D019154:Protein Splicing / Q000235:genetics; D051381:Rats; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
chemical_list: C496972:Kcna2 protein, rat; D051663:Kv1.2 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel