CLONING AND EXPRESSION OF A HUMAN LARGE-CONDUCTANCE CALCIUM-ACTIVATEDPOTASSIUM CHANNEL

A putative BK channel gene was cloned from a human brain (substantia n igra) cDNA library by hybridization screening. The sequence of the ful l length clone shows high homology with the mSlo gene, suggesting that this cDNA is the human homologue (hSlo). The hSlo clone does not cont ain either alternative exon A or B at its splice sites; and similar to mSlo, it has a long string of serines at its 5' end. Reverse transcri ption coupled with the PCR technique demonstrated the differences in e xpression of the isoforms among the CNS and the periphery. Expression of hSlo in Xenopus oocytes showed a family of outward currents, induce d by step depolarizations, that were blocked by iberiotoxin and activa ted by the compound NS004, a known opener of native and cloned maxi-K channels. Single channel recordings of hSlo channels showed a high deg ree of voltage- and Ca2+-dependence. and an average single channel con ductance of 285.9 pS.