CLONING, EXPRESSION, AND DISTRIBUTION OF FUNCTIONALLY DISTINCT CA2-ACTIVATED K+ CHANNEL ISOFORMS FROM HUMAN BRAIN()

We have cloned and expressed nine Ca2+-activated K+ channel isoforms f rom human brain. The open reading frames encode proteins ranging from 1154 to 1195 amino acids, and all possess significant identity with th e slowpoke gene products in Drosophila and mouse. All isoforms are gen erated by alternative RNA splicing of a single gene on chromosome 10 a t band q22.3 (hslo). RNA splicing occurs at four sites located in the carboxyterminal portion of the protein and gives rise to at least nine ion channel constructs (hbr1-hbr9). hslo mRNA is expressed abundantly in human brain, and individual isoforms show unique expression patter ns. Expression of hslo mRNA in Xenopus oocytes produces robust voltage and Ca2+-activated K+ currents. Splice variants differ significantly in their Ca2+ sensitivity, suggesting a broad functional role for thes e channels in the regulation of neuronal excitability.