Voltage-dependent potassium currents exhibit specific time tables of functional differentiation and regulate the development of action potentials in amphibian spinal neurons. A Xenopus nucleotide sequence (XSha2) encoding a potassium current has been isolated by homology screening with the Drosophila Shaker gene. Functional expression in oocytes identifies it as a delayed rectifier. Southern analysis suggests that XSha2 is a member of a family of highly related genes. XSha2 is expressed in the nervous system but is not detectable in skeletal muscle. Transcripts are apparent at the neural fold stage, and subsequent levels parallel those of the neural marker N-CAM. Thus molecular events required for the establishment of electrical excitability in the vertebrate embryo occur early during neurogenesis.