Subunit composition of Kv1 channels in human CNS

The alpha subunits of Shaker-related K+ channels (Kv1.X) show characteristi c distributions in mammalian brain and restricted coassembly. Despite the f unctional importance of these voltage-sensitive K+ channels and involvement in a number of diseases, little progress has been achieved in deciphering the subunit composition of the (alpha)(4)(beta)(4) oligomers occurring in h uman CNS. Thus, the association of alpha and beta subunits was investigated in cerebral grey and white matter and spinal cord from autopsy samples. Im munoblotting established the presence of Kv1.1, 1.2, and 1.4 in all the tis sues, with varying abundance. Sequential immunoprecipitations identified th e subunits coassembled. A putative tetramer of Kv1.3/1.4/1.1/1.2 was found in grey matter. Both cerebral white matter and spinal cord contained the he terooligomers Kv1.1/1.4 and Kv1.1/1.2, similar to grey matter, but both lac ked Kv1.3 and the Kv1.4/1.2 combination. An apparent Kv1.4 homooligomer was detected in all the samples, whereas only the brain tissue possessed a put ative Kv1.2 homomer. In grey matter, KV beta 2.1 was coassociated with the Kv1.1/1.2 combination and Kv1.2 homooligomer. In white matter, Kv beta 2.1 was associated with Kv1.2 only, whereas Kv beta 1.1 coprecipitated with all the alpha subunits present. This represents the first description of Kv1 s ubunit complexes in the human CNS and demonstrates regional variations, ind icative of functional specialisation.