Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium

Shaker-related voltage-gated potassium (Rv) channels may be heterooligomers consisting of membrane-integral cu-subunits associated with auxiliary cytoplasmic p-subunits, In this study we have cloned the human Kv beta 3.1 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 Kv beta genes have very disparate lengths varying from greater than or equal to 350 kb (KCNA1B) to similar to 7 kb (KCNA3B). Yet, the exon patterns of the three genes, which code for the seven known mammalian Kv beta subunits, are very similar. The Kv beta 1 and Kv beta 2 splice variants are generated by alternative use of 5'-exons. Mouse Rv beta 4, a potential splice variant of Kv beta 3, is a read-through product where the open reading frame starts within the sequence intervening between Kv beta 3 exons 7 and 8, The human KCNA3B sequence does not contain a mouse Kv beta 4-like open reading frame. Human Kv beta 3 mRNA is specifically expressed in the brain, where it is predominantly detected in the cerebellum. The heterologous coexpression of human Kv1.5 and Kv beta 3.1 subunits in Chinese hamster ovary cells yielded a novel Ky channel mediating very fast inactivating (A-type) outward currents upon depolarization. Thus, the expression of Kv beta 3.1 subunits potentially extends the possibilities to express diverse A-type Kv channels in the human brain.