Mammalian central neurons regulate a diverse set of functions by changes in spatial and temporal expression patterns of a large family of K+ channel gene products. Here the temporal patterns of expression of Kv2.1 (drk1) K+ channel mRNAs and polypeptides have been studied in rat brain. Northern blots using Kv2.1-specific probes show that three size classes (4.4, 9.0, 11.5 kb) of Kv2.1 K+ channel transcripts are present in rat brain. These mRNAs show differential patterns of expression over embryonic and postnatal developmental, with the 4.4 kb transcript being the predominant embryonic Kv2.1 mRNA, and the 11.5 kb transcript being the predominant adult mRNA. Immunoblots using Kv2.1-specific site-directed antibodies show the existence of multiple Kv2.1 polypeptides, which differ in their mobility on SDS polyacrylamide gels, in their immunoreactivity to a carboxyl terminal-directed anti-Kv2.1 antibody, and in their developmental expression. Thus Kv2.1 polypeptide isoforms exhibit discrete temporal patterning during neuronal development, implying distinct roles for these channel proteins in vivo.