STRUCTURAL AND FUNCTIONAL-CHARACTERIZATION OF HUMAN POTASSIUM CHANNELSUBUNIT BETA-1 (KCNA1B)

Voltage-activated Shaker-related potassium channels (K(v)1) consist of alpha and beta subunits. We have analysed the structure of the human KCNA1B (hK(v) beta 1) gene. KCNA1B is >250 kb in size and encodes at l east three K-v beta 1 splice variants. The K-v beta 1 open reading fra me is divided into 14 exons. In contrast, genes coding for family memb ers of KCNA (K(v)1 alpha) subunits are markedly smaller and have intro nless open reading frames. The expression of K(v)1 alpha and K-v beta mRNA was compared in Northern blots of poly(A(+)) RNA isolated from va rious human brain tissues. The results suggest an intricate and cell-s pecific regulation of K(v)1 alpha and K-v beta mRNA synthesis such tha t distinct combinations of alpha and beta subunits would occur in diff erent nuclei of the brain. The splice variants hK(v) beta 1.1 and hK(v ) beta 1.2 were functionally characterized in coexpression studies wit h hK(v)1.5 alpha subunits in 293 cells. It is shown that they confer r apid inactivation on hK(v)1.5 channels with different potencies. This may be due to differences in their amino terminal sequences and/or ina ctivating domains. It is also shown that the amino terminal K-v beta 1 .1 and K(v)1.4 alpha inactivating domains compete with each other, pro bably for the binding to the same receptor site(s) on K(v)1 alpha-subu nits. Copyright (C) 1996 Elsevier Science Ltd