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

Shaker-related voltage-gated potassium (Rv) channels may be heterooligomers consisting of membrane-integral cu-subunits associated with auxiliary cyto plasmic p-subunits, In this study we have cloned the human Kv beta 3.1 subu nit and the corresponding KCNA3B gene. Identification of sequence-tagged si tes in the gene mapped KCNA3B to band p13.1 of human chromosome 17. Compari son of the KCNA1B, KCNA2B, and KCNA3B gene structures showed that the three Kv beta genes have very disparate lengths varying from greater than or equ al to 350 kb (KCNA1B) to similar to 7 kb (KCNA3B). Yet, the exon patterns o f the three genes, which code for the seven known mammalian Kv beta subunit s, are very similar. The Kv beta 1 and Kv beta 2 splice variants are genera ted by alternative use of 5'-exons. Mouse Rv beta 4, a potential splice var iant of Kv beta 3, is a read-through product where the open reading frame s tarts 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 i t is predominantly detected in the cerebellum. The heterologous coexpressio n of human Kv1.5 and Kv beta 3.1 subunits in Chinese hamster ovary cells yi elded 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.