Coexpression of the KCNA3B Gene Product with Kv1.5 Leads to a Novel A-type Potassium Channel

Shaker -related voltage-gated potassium (Kv) channels may be heterooligomers consisting of membrane-integral α-subunits associated with auxiliary cytoplasmic β-subunits. In this study we have cloned the human Kvβ3.1 subunit and the corresponding KCNA3B gene. Identification of sequence-tagged sites in the gene mapped KCNA3B to band p13.1 of human chromosome 17. Comparison of the KCNA1B , KCNA2B , and KCNA3B gene structures showed that the three Kvβ genes have very disparate lengths varying from ≥350 kb ( KCNA1B ) to ∼7 kb ( KCNA3B ). Yet, the exon patterns of the three genes, which code for the seven known mammalian Kvβ subunits, are very similar. The Kvβ1 and Kvβ2 splice variants are generated by alternative use of 5′-exons. Mouse Kvβ4, a potential splice variant of Kvβ3, is a read-through product where the open reading frame starts within the sequence intervening between Kvβ3 exons 7 and 8. The human KCNA3B sequence does not contain a mouse Kvβ4-like open reading frame. Human Kvβ3 mRNA is specifically expressed in the brain, where it is predominantly detected in the cerebellum. The heterologous coexpression of human Kv1.5 and Kvβ3.1 subunits in Chinese hamster ovary cells yielded a novel Kv channel mediating very fast inactivating (A-type) outward currents upon depolarization. Thus, the expression of Kvβ3.1 subunits potentially extends the possibilities to express diverse A-type Kv channels in the human brain.