A Functional Spliced-Variant of β2 Subunit of Kv1 Channels in C6 Glioma Cells and Reactive Astrocytes from Rat Lesioned Cerebellum

• Published in: Biochemistry (Easton) Vol. 38; no. 51; pp. 16984 - 16992
• Main Authors: Akhtar, Sobia, McIntosh, Paul, Bryan-Sisneros, Andrea, Barratt, Lynne, Robertson, Brian, Dolly, J. Oliver
• Format: Journal Article
• Language: English
• Published: American Chemical Society 21.12.1999
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi992114x

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 α plus β1.1 subunits, as well as an unusual β2.1 constituent; the latter was also found in a glioblastoma C6 cell line, together with Kv1.1, -1.3, and -1.6 and β1.1 subunits. Reverse transcriptase−polymerase chain reaction revealed a novel product of the β2 gene in C6 cells and reactive astrocytes, but not in cultured astrocytes or rat normal brain. Its cloning identified a variant, Kvβ2.1A, alternatively spliced between I24 and Y39. Despite this 14 residue deletion, Kvβ2.1A 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 β2.1 gave a large increase in the amplitude of the Kv1.1 current in oocytes, the effect of β2.1A 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 Kvβ2.1 gene in C6 cells and reactive astrocytes, and supports the involvement of its core region (residues 39 onward) in assembly with α subunits while excluding a contribution of the adjacent 14 residues to accelerating the inactivation of Kv1.4.