A functional spliced-variant of beta 2 subunit of Kv1 channels in C6 glioma cells and reactive astrocytes from rat lesioned cerebellum

Voltage-gated K+ channels (Kv1) are important in glia, being required for c ell 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 beta 1. 1 subunits, as well as an unusual beta 2.1 constituent; the latter was also found in a glioblastoma C6 cell line, together with Kv1.1, -1.3, and -1.6 and beta 1.1 subunits. Reverse transcriptase-polymerase chain reaction reve aled a novel product of the beta 2 gene in C6 cells and reactive astrocytes , but not in cultured astrocytes or rat normal brain. Its cloning identifie d a variant, KV beta 2.1A, alternatively spliced between I24 and Y39. Despi te this 14 residue deletion, KV beta 2.1A assembled cotranslationally with Kv1.1 or -1.2 and when coexpressed with Kv1.4 in oocytes, increased the ina ctivation rate of this K+ current. Whereas the full-length beta 2.1 gave a large increase in the amplitude of the Kv1.1 current in oocytes, the effect of beta 2.1A varied from a modest elevation of the current to a slight sup pression in some cases. In summary, this is the first report of the existen ce of an alternatively spliced product of the Kv beta 2.1 gene in C6 cells and reactive astrocytes. and supports the involvement of its core region (r esidues 39 onward) in assembly with Or subunits while excluding a contribut ion of the adjacent 14 residues to accelerating the inactivation of Kv1.4.